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Shokry AA, Bashir DW, Gamil NM, Nabil G. In-depth molecular assessment of Hedera helix's L. α - Hederin & Hederacoside C as a gastroprotective & a possible safe Omeprazole phyto-alternative in ethanol-induced gastric ulcer mice model. Int Immunopharmacol 2025; 156:114541. [PMID: 40273670 DOI: 10.1016/j.intimp.2025.114541] [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: 02/14/2025] [Revised: 03/08/2025] [Accepted: 03/20/2025] [Indexed: 04/26/2025]
Abstract
Hedera helix L. is among the most popular over-the-counter formulations for effectively alleviating respiratory disorders in adults & children due to its unique active constituents such as α - Hederin & Hederacoside C. Even though its respiratory pharmacological activity is thoroughly researched, its other pharmacological activities remain relatively unexplored. Alcoholism is a Western cultural habit that is associated with various side effects, including peptic ulcer disease (PUD) & drug interaction. The PUD is commonly & recurrently presented clinically, increasing the load on healthcare systems. PUD not only negatively affects the quality of life but is also associated with serious complications such as bleeding, penetration, perforation, pyloric stenosis, & gastric cancer. Alcohol interaction with drugs could either lead to therapeutic failure, accumulation of drug-toxic metabolites, or disturbance of the alcohol detoxification pathway, putting the treatment of alcoholism-induced PUD with a drug-interacting medication such as Omeprazole under the limelight. In line with that, finding plant-derived molecules with the potency of Omeprazole but without its associated side effects & drug-interacting property is a desperate clinical need. In this regard, we aimed to investigate the gastroprotective effect, potency, & molecular mechanism of α - Hederin & Hederacoside C pretreatment against ethanol-induced gastric ulcer in mice model. These compounds were tested in two upgrading doses (50 mg/kg & 75 mg/kg) compared to negative, positive, & Omeprazole groups. Our study revealed that daily oral administration of α - Hederin or Hederacoside C protected the stomach against ethanol-induced gastric ulcers in a dose-dependent manner. The potency of high doses of both compounds was comparable to Omeprazole. Their effectiveness was related to their ability to set the activated invasive forces, including CYP1A2, neutrophils, MDA, leptin, TNF-α, IL-6, IL-12, & NF-κB-p65 & to amplify the intrinsic defensive forces, including COX-2, PGE-2, CAT, & SOD. These intertwined actions were reflected in maintaining vibrant stomach architecture, such as mucosal layer re-epithelization, gland reconstruction, & restoring tunica muscularis normal thickness. Moreover, they limited the exaggeration of the repairing system, including HSP-70, VEGF, & Annexin-1, where their forge was positively correlated with damage depth. Therefore, we compendiously deduced that herbal-based medicine could face the constraints of synthesized medicine satisfactorily without their culminating side effects.
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Affiliation(s)
- Aya A Shokry
- Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt.
| | - Dina W Bashir
- Department of Cytology & Histology, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt
| | - Noha M Gamil
- Department of Pharmacology & Toxicology, College of Pharmaceutical Sciences & Drug Manufacturing, Misr University for Science & Technology (MUST), Giza P.O. Box 77, Egypt
| | - Ghazal Nabil
- Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt.
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Cerda IH, Jung H, Guerrero MC, Diez Tafur R, Yong RJ, Robinson CL, Hasoon JJ. Trends in Celecoxib Prescribing: A Single Institution 16-Month Review. J Clin Med 2025; 14:2823. [PMID: 40283653 PMCID: PMC12028116 DOI: 10.3390/jcm14082823] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2025] [Revised: 04/14/2025] [Accepted: 04/16/2025] [Indexed: 04/29/2025] Open
Abstract
Background/Objectives: Celecoxib, a COX-2 selective nonsteroidal anti-inflammatory drug (NSAID), is widely prescribed for pain management due to its efficacy and improved gastrointestinal safety profile compared to traditional NSAIDs. Understanding prescription trends and their comparison to other NSAIDs provides valuable insight into prescribing behaviors in clinical settings. Methods: This retrospective study analyzed celecoxib prescriptions written by three pain management physicians in a single institution over a 16-month period from 1 January 2023 to 30 April 2024. Prescription data were collected and grouped into four 4-month intervals to assess temporal trends. Additionally, we compared celecoxib prescriptions to other commonly prescribed NSAIDs, including ibuprofen, meloxicam, naproxen, and diclofenac. Results: A total of 143 celecoxib prescriptions were identified during the study period, with a steady increase observed across consecutive intervals: 8 prescriptions from January-April 2023, 22 from May-August 2023, 46 from September-December 2023, and 67 from January-April 2024. In comparison, a total of 165 prescriptions were written for other NSAIDs over the same period, with 26 prescriptions from January-April 2023, 41 from May-August 2023, 45 from September-December 2023, and 53 from January-April 2024. While prescriptions for both celecoxib and other NSAIDs increased over time, the rate of celecoxib prescriptions showed a steeper rise. Conclusions: The findings demonstrate a notable increase in celecoxib prescriptions in this pain management clinic, outpacing the growth of other NSAIDs. This trend may reflect increasing provider preference for COX-2 selective inhibitors due to their favorable safety profile and efficacy. Further research is warranted to explore the underlying factors driving these prescribing patterns.
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Affiliation(s)
| | - Helen Jung
- Albert Einstein College of Medicine, Bronx, NY 10461, USA
| | - Maria C. Guerrero
- Department of Physical Medicine & Rehabilitation, Larking Community Hospital, South Miami, FL 33143, USA
| | - Rodrigo Diez Tafur
- Pain Management Unit, Clínica Angloamericana, San Isidro 15073, Peru
- Centro MDRS: Sports, Spine & Pain Centers, Miraflores 15073, Peru
| | - Robert Jason Yong
- Department of Anesthesiology, Perioperative, and Pain Medicine, Harvard Medical School, Boston, MA 02115, USA; (R.J.Y.); (C.L.R.)
| | - Christopher L. Robinson
- Department of Anesthesiology, Perioperative, and Pain Medicine, Harvard Medical School, Boston, MA 02115, USA; (R.J.Y.); (C.L.R.)
| | - Jamal J. Hasoon
- Department of Anesthesia, Critical Care, and Pain Medicine, UTHealth, McGovern Medical School, Houston, TX 77030, USA
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Ukpeh IE, Akpan MI, Ugbe UMJ, Enyievi PB, Osuchukwu NC, Bassey EE, Yolo SB. Predictors of blood pressure control among patients with hypertension: a cross-sectional study in a Nigerian tertiary health facility. BMJ Open 2025; 15:e091010. [PMID: 40107702 PMCID: PMC11927482 DOI: 10.1136/bmjopen-2024-091010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Accepted: 03/03/2025] [Indexed: 03/22/2025] Open
Abstract
BACKGROUND Adequate blood pressure control improves clinical outcomes in patients with hypertension. Poor blood pressure control is linked with cardiovascular diseases and poor quality of life. AIM To identify the predictors of blood pressure control among patients with hypertension treated at the University of Calabar Teaching Hospital, Calabar, Nigeria. METHODS This was a descriptive, cross-sectional study that recruited 441 hypertensive adults who were on medications for at least 6 months through systematic random sampling. Data were analysed using bivariate and multivariate methods at 95% CI and α=0.05. Blood pressure was measured twice using a mercury sphygmomanometer, with averages recorded. RESULTS The average age of participants was 55.46 years±12.91. About 48.1% of respondents achieved adequate blood pressure control. Major reported risk factors of inadequate blood pressure control were sedentary lifestyle (67.8%), use of caffeinated drinks (51.9%) and family history of hypertension (47.5%). The major comorbidities of hypertension were gastrointestinal symptoms (46.72%) and diabetes (31.39%). The predictors of adequate blood pressure control were higher income (adjusted OR (AOR)=2.94, p=0.026), full health insurance (AOR=2.32, p=0.030), non-usage of caffeinated drinks (AOR=4.13, p=0.001) and normal body mass index (AOR=1.63, p=0.026). Predictors of inadequate blood pressure control were older age (AOR=0.30, p<0.001), living with a spouse (AOR=0.14, p=0.014), non-compliance with antihypertensive medications (AOR=0.53, p=0.040) and moderate obesity (AOR=0.29, p=0.032). CONCLUSION Addressing prevalent risk factors like sedentary lifestyle and dietary habits, as well as structural initiatives like accessibility to health insurance, presents opportunities for targeted interventions to enhance well-being and improve outcomes that will strengthen public health, clinical practice and research.
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Affiliation(s)
- Ido Edem Ukpeh
- Cardiology Unit, Department of Internal Medicine, University of Calabar Teaching Hospital, Calabar, Cross River, Nigeria
- Faculty of Clinical Sciences, Department of Internal Medicine, University of Calabar Teaching Hospital, Calabar, Cross River, Nigeria
| | | | - Ugbe Maurice-Joel Ugbe
- Public Health, University of Calabar, Calabar, Cross River, Nigeria
- Center of Excellence for Human Resource for Health and Training, University of Calabar, Calabar, Cross River, Nigeria
| | | | | | - Ekpenyong Eyo Bassey
- Cardiology Unit, Department of Internal Medicine, University of Calabar Teaching Hospital, Calabar, Cross River, Nigeria
| | - Smith Bakumor Yolo
- Cardiology Unit, Department of Internal Medicine, University of Calabar Teaching Hospital, Calabar, Cross River, Nigeria
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Wally ME, Aly MH. Gastroprotective Effect of Linagliptin on Indomethacin-Induced Gastric Ulceration in Mice: Crosstalk Between Oxidative Stress and Inflammasome Pathways. ACS Pharmacol Transl Sci 2025; 8:808-818. [PMID: 40109745 PMCID: PMC11915470 DOI: 10.1021/acsptsci.4c00695] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2024] [Revised: 02/20/2025] [Accepted: 02/25/2025] [Indexed: 03/22/2025]
Abstract
The clinical efficacy of indomethacin, a nonsteroidal anti-inflammatory drug, is hindered by its high ulcerogenic potential. Linagliptin, a dipeptidyl peptidase-4 inhibitor, has demonstrated anti-inflammatory properties through NLRP3 inflammasome modulation; however, its possible antiulcerogenic effect remains unclear. This study aimed to examine the potential prophylactic effect of linagliptin against indomethacin-induced gastric ulcers with a focus on NLRP3 inflammasome signaling. Gastric ulcers were induced using indomethacin and compared to pretreatment with linagliptin or the standard prophylactic omeprazole. Gastric injury was confirmed by gross morphology, ulcer scoring, and histopathological assessments. Additionally, redox status markers glutathione reductase (GSH), malondialdehyde (MDA), and Nrf2/Keap-1/HO-1 were evaluated in the gastric tissue. Immunohistochemical analysis of pNF-κB, NLRP3, and Caspase-1 inflammasome parameters was also conducted. Finally, measurement of gastric levels of Gasdermin-D was performed, as well as immunohistochemical and gene expression of IL-1β. Pretreatment with linagliptin suppressed all features of mucosal damage as well as inflammatory cell infiltration. The antioxidant effect of linagliptin was evident in low MDA, high GSH gastric levels, and high immunohistochemical reactivity of gastric tissues against Nrf2 and HO-1 antibodies, as well as low gastric levels of keap1. The overly active inflammasome pathway observed in indomethacin-induced ulcerated samples was reinstated by linagliptin, as seen in the suppression of pNF-κB, NLRP3, Caspase-1, and IL-1β immunohistochemical reactivity as well as Gasdermin-D levels. Our study showed that NLRP3 inflammasome contributes to the pathogenesis of indomethacin-mediated gastric injury and that linagliptin exhibits a protective effect against indomethacin-induced gastric ulcers, possibly through activation of the Nrf2/HO-1 antioxidant pathway and inhibition of the NLRP3 inflammasome axis.
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Affiliation(s)
- Maha E Wally
- Pharmacology Department, Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, Cairo 11837, Egypt
- Health Research Center of Excellence; Drug Research and Development Group, Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, Cairo 11837, Egypt
| | - Mohamed H Aly
- Pharmacology Department, Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, Cairo 11837, Egypt
- Health Research Center of Excellence; Drug Research and Development Group, Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, Cairo 11837, Egypt
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Elgohary MK, Elkotamy MS, Alkabbani MA, El Hassab MA, Al-Rashood ST, Binjubair FA, Alsulaimany M, Ghabbour HA, Eldehna WM, Abdel-Aziz HA. Sulfonamide-Pyrazole derivatives as next-generation Cyclooxygenase-2 enzyme inhibitors: From molecular design to in vivo efficacy. Int J Biol Macromol 2025; 293:139170. [PMID: 39736293 DOI: 10.1016/j.ijbiomac.2024.139170] [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: 11/10/2024] [Revised: 12/19/2024] [Accepted: 12/23/2024] [Indexed: 01/01/2025]
Abstract
The current research focuses on the design and synthesis of celecoxib analogues incorporating sulphonamide and pyrazole moieties (4, 5, 6a-e, and 7a-f) with the aim of achieving a broad range of COX-2 selectivity in vitro. Among these, compounds 6b-d, 7a, 7e, and 7d exhibited potent inhibition, with IC50 values ranging between 0.05 and 0.08 μM, and were selected for in vivo evaluation using the formalin-induced paw edema model. To further assess the safety profile of compound 6d, a histopathological examination of paw tissue was conducted alongside routine blood analyses evaluating key liver and kidney function parameters, including creatinine, urea, AST, and ALT levels. The results indicated normal profiles, comparable to reference drugs celecoxib and indomethacin. Additionally, compound 6d was evaluated for its effect on inflammatory biomarkers using ELISA assays. Markedly, 6d elicited a remarkable reduction in TNF-α (71.43 %) and PGE2 (77.11 %) levels, surpassing the effects of both celecoxib and indomethacin, confirming its potent anti-inflammatory properties. In terms of analgesic activity, Importantly, cardiac toxicity assessment revealed no adverse effects associated with compound 6d. Finally, compound 6d underwent in silico analysis, including molecular docking and molecular dynamics simulations, which confirmed its selective interaction with the COX-2 active site and favorable free insertion into the selectivity side pocket.
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Affiliation(s)
- Mohamed K Elgohary
- Pharmaceutical Chemistry Department, Faculty of Pharmacy, Egyptian-Russian University, Badr City, Cairo 11829, Egypt.
| | - Mahmoud S Elkotamy
- Pharmaceutical Chemistry Department, Faculty of Pharmacy, Egyptian-Russian University, Badr City, Cairo 11829, Egypt
| | - Mahmoud Abdelrahman Alkabbani
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Egyptian-Russian University, Badr City, Cairo 11829, Egypt
| | - Mahmoud A El Hassab
- Department of Medicinal Chemistry, Faculty of Pharmacy, King Salman International University (KSIU), South Sinai, Egypt
| | - Sara T Al-Rashood
- Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia
| | - Faizah A Binjubair
- Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia
| | - Marwa Alsulaimany
- Department of Pharmacognosy & Pharmaceutical Chemistry, College of Pharmacy, Taibah University, Medina 42353, Saudi Arabia
| | - Hazem A Ghabbour
- School of Health and Biomedical Sciences, RMIT University, Melbourne 3083, Australia
| | - Wagdy M Eldehna
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, P.O. Box 33516, Egypt
| | - Hatem A Abdel-Aziz
- Applied Organic Chemistry Department, National Research Center, Dokki, Cairo 12622, Egypt; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Pharos University in Alexandria, Canal El Mahmoudia St., Alexandria 21648, Egypt.
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Ballard ET, Bergeson KS, Wisniewski SJ, Singh S, Ejub S, Nelson RA. Gastrointestinal Bleeds Are a Rare Event After Total Hip and Knee Arthroplasty. J Arthroplasty 2025:S0883-5403(25)00098-1. [PMID: 39892621 DOI: 10.1016/j.arth.2025.01.047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2024] [Revised: 01/23/2025] [Accepted: 01/24/2025] [Indexed: 02/04/2025] Open
Abstract
BACKGROUND The presence of a gastrointestinal (GI) bleed after elective total hip arthroplasty and total knee arthroplasty (THA and TKA, respectively) is concerning and a potential cause for hospital readmission. This condition can also be life-threatening if not identified and treated appropriately. Many surgeons use multimodal analgesia protocols to limit opioid use and also use venous thromboembolism prophylaxis. Aspirin and nonsteroidal anti-inflammatories, often a component of these protocols, reduce prostaglandin production necessary for gastric mucosal protection. The authors hypothesized that the incidence of a GI bleed after TKA and THA would be rare. METHODS This was a retrospective review of 8,207 patients 18 years or older who had THA or TKA at a single institution between 2015 and 2022. Patients who were evaluated for GI bleed within 90 days postoperatively were identified. Perioperative risks were analyzed based on demographics, procedures, and other risk factors. RESULTS The incidence of GI bleeding was 0.33%, in which 27 patients sustained a GI bleed in 8,206 THA and TKA cases. The average days from the time of surgery for GI bleed were 18.6 days. There was a difference in the occurrence of GI bleeds by age, with increasing age being positively associated with an increase in the odds of GI bleeds, odds ratio = 1.15 (95% CI [confidence interval]: 1.09 to 1.21), P < 0.01. No statistical difference was found based on other demographic data, procedure type, or site. CONCLUSIONS This institution's perioperative protocol, including the use of nonsteroidal anti-inflammatories and aspirin for TKA and THA, had a low incidence of GI bleeds in the perioperative setting at our community hospital over the course of 2015 to 2022.
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Affiliation(s)
- Eric T Ballard
- Orthopaedic Surgery Department, Henry Ford Genesys Hospital, Grand Blanc, Michigan; Michigan State University College of Osteopathic Medicine, East Lansing, Michigan
| | - Keifer S Bergeson
- Orthopaedic Surgery Department, Henry Ford Genesys Hospital, Grand Blanc, Michigan; Michigan State University College of Osteopathic Medicine, East Lansing, Michigan
| | | | - Sahiba Singh
- Michigan State University College of Osteopathic Medicine, East Lansing, Michigan
| | - Sabit Ejub
- Orthopaedic Surgery Department, Henry Ford Genesys Hospital, Grand Blanc, Michigan; Michigan State University College of Osteopathic Medicine, East Lansing, Michigan
| | - Ryan A Nelson
- Orthopaedic Surgery Department, Henry Ford Genesys Hospital, Grand Blanc, Michigan
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Kumar P, Kinger S, Dubey AR, Jagtap YA, Choudhary A, Karmakar S, Lal G, Kumar A, Bhattacharyya S, Poluri KM, Mishra A. Ketorolac disturbs proteasome functions and induces mitochondrial abnormality-associated apoptosis. IUBMB Life 2025; 77:e2937. [PMID: 39723629 DOI: 10.1002/iub.2937] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Accepted: 12/11/2024] [Indexed: 12/28/2024]
Abstract
Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended to treat moderate-to-severe pain. Previous studies suggest that NSAIDs can suppress cellular proliferation and elevate apoptosis in different cancer cells. Ketorolac is an NSAID and can reduce the cancer cells' viability. However, molecular mechanisms by which Ketorolac can induce apoptosis and be helpful as an anti-tumor agent against carcinogenesis are unclear. Here, we observed treatment with Ketorolac disturbs proteasome functions, which induces aggregation of aberrant ubiquitinated proteins. Ketorolac exposure also induced the aggregation of expanded polyglutamine proteins, results cellular proteostasis disturbance. We found that the treatment of Ketorolac aggravates the accumulation of various cell cycle-linked proteins, which results in pro-apoptotic induction in cells. Ketorolac-mediated proteasome disturbance leads to mitochondrial abnormalities. Finally, we have observed that Ketorolac treatment depolarized mitochondrial membrane potential, released cytochrome c into cytoplasm, and induced apoptosis in cells, which could be due to proteasome functional depletion. Perhaps more in-depth research is required to understand the details of NSAID-based anti-proliferative molecular mechanisms that can elevate apoptosis in cancer cells and generate anti-tumor potential with the combination of putative cancer drugs.
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Affiliation(s)
- Prashant Kumar
- Cellular and Molecular Neurobiology Unit, Indian Institute of Technology Jodhpur, Jodhpur, Rajasthan, India
| | - Sumit Kinger
- Cellular and Molecular Neurobiology Unit, Indian Institute of Technology Jodhpur, Jodhpur, Rajasthan, India
| | - Ankur Rakesh Dubey
- Cellular and Molecular Neurobiology Unit, Indian Institute of Technology Jodhpur, Jodhpur, Rajasthan, India
| | - Yuvraj Anandrao Jagtap
- Cellular and Molecular Neurobiology Unit, Indian Institute of Technology Jodhpur, Jodhpur, Rajasthan, India
| | - Akash Choudhary
- Cellular and Molecular Neurobiology Unit, Indian Institute of Technology Jodhpur, Jodhpur, Rajasthan, India
| | - Surojit Karmakar
- National Centre for Cell Science (NCCS), Pune, Maharashtra, India
| | - Girdhari Lal
- National Centre for Cell Science (NCCS), Pune, Maharashtra, India
| | - Amit Kumar
- Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, Madhya Pradesh, India
| | - Sudipta Bhattacharyya
- Department of Bioscience and Bioengineering, Indian Institute of Technology Jodhpur, Jodhpur, Rajasthan, India
| | - Krishna Mohan Poluri
- Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand, India
| | - Amit Mishra
- Cellular and Molecular Neurobiology Unit, Indian Institute of Technology Jodhpur, Jodhpur, Rajasthan, India
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Cruz-Antonio L, Sánchez-Mendoza ME, García-Machorro J, López-Lorenzo Y, Arrieta J. Study of the Effect of Methyl Eugenol on Gastric Damage Produced by Spinal Cord Injury Model in the Rat. Molecules 2024; 30:86. [PMID: 39795143 PMCID: PMC11721453 DOI: 10.3390/molecules30010086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Revised: 12/18/2024] [Accepted: 12/26/2024] [Indexed: 01/13/2025] Open
Abstract
Traumatic spinal cord injury (SCI) is a serious medical condition that places patients at high risk of developing gastric ulceration and gastrointestinal bleeding. One preventative strategy involves the use of omeprazole; however, its chronic use is associated with adverse effects, highlighting the need for alternative therapies. This study evaluated the protective effects of methyl eugenol (ME) on gastric mucosal damage in a rat model of SCI. ME was administered orally at doses of 30, 100, and 177 mg/kg in SCI induced at the T9 level, alongside diclofenac or ketorolac (30 mg/kg each). The enzymatic activity of superoxide dismutase, catalase, and glutathione peroxidase was assessed, and the levels of total glutathione and malondialdehyde were determined using biochemical kits. Additionally, stomach histological sections were analyzed. ME exhibited dose-dependent gastroprotective effects, with maximal protection observed at 177 mg/kg in the presence of diclofenac (9.78 ± 2.16 mm2) or ketorolac (12.49 ± 2.17 mm2). A histological analysis confirmed these findings. In conclusion, methyl eugenol protects the gastric mucosa from SCI-induced damage, with glutathione peroxidase and catalase playing key roles in its mechanism of gastroprotection.
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Affiliation(s)
- Leticia Cruz-Antonio
- Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México (UNAM), Av. Guelatao No. 66, Colonia Ejército de Oriente, Iztapalapa, Ciudad de México 09230, Mexico;
| | - María Elena Sánchez-Mendoza
- Laboratorio de Farmacología de Plantas Medicinales Mexicanas, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, Colonia Casco de Santo Tomás, Miguel Hidalgo, Ciudad de México 11340, Mexico; (M.E.S.-M.); (Y.L.-L.)
| | - Jazmín García-Machorro
- Laboratorio de Medicina de la Conservación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, Colonia Casco de Santo Tomás, Miguel Hidalgo, Ciudad de México 11340, Mexico;
| | - Yaraset López-Lorenzo
- Laboratorio de Farmacología de Plantas Medicinales Mexicanas, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, Colonia Casco de Santo Tomás, Miguel Hidalgo, Ciudad de México 11340, Mexico; (M.E.S.-M.); (Y.L.-L.)
| | - Jesús Arrieta
- Laboratorio de Farmacología de Plantas Medicinales Mexicanas, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, Colonia Casco de Santo Tomás, Miguel Hidalgo, Ciudad de México 11340, Mexico; (M.E.S.-M.); (Y.L.-L.)
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Velasco-Velasco F, Llerena-Velastegui J. Advances and results in omental patch repair of gastrointestinal perforations: A narrative review. SURGERY IN PRACTICE AND SCIENCE 2024; 19:100261. [PMID: 39844949 PMCID: PMC11750027 DOI: 10.1016/j.sipas.2024.100261] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Revised: 09/07/2024] [Accepted: 10/01/2024] [Indexed: 01/24/2025] Open
Abstract
Omental patch repair is a crucial surgical procedure for managing gastrointestinal perforations, particularly those associated with peptic ulcers, necessitating a detailed review of its effectiveness and outcomes. This literature review aims to assess current knowledge on omental patch repair, focusing on advancements in surgical techniques and patient outcomes. Major medical databases, including PubMed, Scopus, and Web of Science, were searched for relevant studies published between 2020 and 2024, prioritizing those that explored omental patch repair, surgical methods, and associated clinical outcomes. The results provide insights into the pathophysiology of gastrointestinal perforations, the effectiveness of omental patch repair in promoting healing, and its role in reducing postoperative complications. Both open and laparoscopic techniques have demonstrated improved patient outcomes, including reduced mortality, morbidity, and faster recovery times. Additionally, alternative methods, such as the use of the falciform ligament, offer comparable efficacy in cases where the omentum is unavailable. This review underscores the importance of omental patch repair as a reliable surgical intervention adaptable to various clinical environments. However, further research is necessary to address gaps in long-term outcomes, particularly regarding recurrence rates and complications, highlighting the need for continued innovation and refinement of techniques to enhance patient care.
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Affiliation(s)
| | - Jordan Llerena-Velastegui
- Medical School, Pontifical Catholic University of Ecuador, Quito, Ecuador
- Research Center, Center for Health Research in Latin America (CISeAL), Quito, Ecuador
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10
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Soares-Bezerra RJ, da Silva Ferreira NC, de Almeida Alves TM, Zani CL, Rosa LH, Calheiros AS, de Souza CZ, Miranda JAA, Lima-Quaresma KRF, Alves LA, da Silva Frutuoso V. The analgesic and gastroprotective activities of the three fungal extracts and their possible correlation with the inhibition of the P2X7 receptor. Biomed Pharmacother 2024; 181:117657. [PMID: 39515112 DOI: 10.1016/j.biopha.2024.117657] [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: 06/17/2024] [Revised: 10/25/2024] [Accepted: 10/28/2024] [Indexed: 11/16/2024] Open
Abstract
P2X7 is a purinergic receptor physiologically activated by extracellular ATP. Its activation induces proinflammatory responses, including cytokine release, reactive oxygen species formation, and cell death. Previous in vivo experimental models demonstrated that P2X7 blockade has anti-inflammatory effects; however, there are no drugs used in clinical therapy that act on the P2X7 receptor. In the context of inflammatory diseases, nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used as the first-line treatment; however, their major side effects include stomach ulcer formation, which increases patient morbidity and mortality. Here, we analyzed for the first time the analgesic and gastroprotective activities of three fungal extracts that showed antagonistic effects on P2X7 in vitro. The Antarctic fungal extracts obtained from Vishniacozyma victoriae, Metschnikowia australis, and Ascomycota sp. were tested in animal models of acute pain and ethanol-induced ulceration. These three extracts reduced paw licking by approximately 50 %, which is related to pain behavior, and reduced the number of stomach ulcers 3-7 times compared with the control (70 % ethanol), making them more efficient than the lansoprazole, an NSAID drug, and Brilliant Blue G (BBG), a known P2X7 antagonist, which only halves the number of ulcers. Furthermore, the extracts also protected the gastric mucosa and significantly reduced the levels of liver and renal enzymes compared with those in the ethanol group. Taken together, the fungal extracts presented both analgesic and possibly anti-inflammatory activities and had a protective effect on the gastric epithelium.
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Affiliation(s)
- Rômulo José Soares-Bezerra
- Laboratory of Cellular Communication, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, RJ 21040-360, Brazil.
| | | | - Tânia Maria de Almeida Alves
- Laboratory of Chemistry of Bioactive Natural Products, René Rachou Research Center, Oswaldo Cruz Foundation, Belo Horizonte, MG 30190-009, Brazil
| | - Carlos Leomar Zani
- Laboratory of Chemistry of Bioactive Natural Products, René Rachou Research Center, Oswaldo Cruz Foundation, Belo Horizonte, MG 30190-009, Brazil
| | - Luiz Henrique Rosa
- Laboratory of Polar Microbiology and Tropical Connections, Federal University of Minas Gerais, Belo Horizonte, MG 31270-901, Brazil
| | - Andrea Surrage Calheiros
- Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, RJ 21040-360, Brazil
| | - Cristiane Zanon de Souza
- Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, RJ 21040-360, Brazil
| | | | | | - Luiz Anastacio Alves
- Laboratory of Cellular Communication, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, RJ 21040-360, Brazil
| | - Válber da Silva Frutuoso
- Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, RJ 21040-360, Brazil
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11
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Elkotamy MS, Elgohary MK, Alkabbani MA, Salem R, Eldehna WM, Abdel-Aziz HA. Spiro-fused indoline-quinazoline hybrids as smart bombs against TNF-α-mediated inflammation. Int J Biol Macromol 2024; 283:137554. [PMID: 39549799 DOI: 10.1016/j.ijbiomac.2024.137554] [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: 09/28/2024] [Revised: 11/05/2024] [Accepted: 11/10/2024] [Indexed: 11/18/2024]
Abstract
Inflammation is central to numerous diseases, highlighting the need for new anti-inflammatory agents. This study explores the potential of novel spirofused indoline-quinazoline hybrids (4a-p) as anti-inflammatory compounds, inspired by a spiroisatin analogue (VI) that showed modest TNF-α inhibition. We aimed to enhance activity by modifying the isatin scaffold: first, introducing N-alkylation (propyl, butyl, or isobutyl) to improve hydrophobic interactions within the TNF-α dimer active site; second, adding halogens (F, Cl, Br) at the 5-position to increase lipophilicity. Anti-inflammatory activity against TNF-α was confirmed in-vivo for all synthesized analogues, with 4b, 4e, 4k, and 4n emerging as the top candidates. Further studies on these four compounds assessed their analgesic effects, as well as their impact on PGE2, NF-κB, paw thickness, and paw weight. In-vitro analyses revealed nanomolar TNFR2-TNF-α binding inhibition for the four leads. Safety evaluations included histopathology, ulcerogenic potential, kidney and liver functions, and acute hemotoxicity. In-silico studies examined drug-likeness, pharmacokinetics, and TNF-α dimer interactions. These results suggest that the four lead compounds possess promising profiles compared to standard therapies.
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Affiliation(s)
- Mahmoud S Elkotamy
- Pharmaceutical Chemistry Department, Faculty of Pharmacy, Egyptian-Russian University, Badr City, Cairo 11829, Egypt.
| | - Mohamed K Elgohary
- Pharmaceutical Chemistry Department, Faculty of Pharmacy, Egyptian-Russian University, Badr City, Cairo 11829, Egypt
| | - Mahmoud Abdelrahman Alkabbani
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Egyptian-Russian University, Badr City, Cairo, 11829, Egypt
| | - Rofaida Salem
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, P.O. Box 33516, Egypt
| | - Wagdy M Eldehna
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, P.O. Box 33516, Egypt.
| | - Hatem A Abdel-Aziz
- Applied Organic Chemistry Department, National Research Center, Dokki, Cairo, 12622, Egypt; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Pharos University in Alexandria, Canal El Mahmoudia St., Alexandria 21648, Egypt.
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12
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Aly MH, Said AK, Farghaly AM, Eldaly DA, Ahmed DS, Gomaa MH, Elgebaly NH, Sameh O, Elahwany SK, Ebrahem TT, Sameh Y, Wally ME. Protective effect of astaxanthin on indomethacin-induced gastric ulcerations in mice. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2024; 397:9897-9907. [PMID: 38940848 PMCID: PMC11582222 DOI: 10.1007/s00210-024-03206-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Accepted: 05/31/2024] [Indexed: 06/29/2024]
Abstract
Gastric ulcer disease remains one of the common medical burdens affecting millions worldwide due to its prevalent risk factors with the chronic usage of non-steroidal anti-inflammatory drugs at the top, reportedly through the stimulation of oxidative stress and triggering of inflammatory and apoptotic cascades in the gastric mucosa. Astaxanthin, a dietary keto-carotenoid derived from marine organisms is gaining a wide interest as a nutraceutical for its pronounced antioxidant properties. Here, we aim to examine the potential modulatory role of astaxanthin on indomethacin-induced gastric ulceration in experimental mice. Twenty-four Swiss albino mice were randomly distributed into four groups: a control group, an indomethacin group, and two groups pre-treated with either omeprazole or astaxanthin. The gastric tissues were assessed using gross morphology, ulcer scoring, gastric juice acidity, as well as reduced glutathione (GSH) and malondialdehyde (MDA) levels. Histopathological examination and immunostaining for nuclear factor-kappa B (NF-κB) and caspase-3 levels were also employed. Indomethacin group tended to show a higher number of mucosal ulcerations relative to control and pre-treated groups. The indomethacin group also showed significantly lower GSH levels and higher MDA levels relative to control. Immunostaining of gastric tissue sections showed a higher reactivity to NF-κB and caspase-3 in indomethacin group. Astaxanthin pre-treatment significantly elevated gastric juice pH, normalized GSH levels, and lowered the indomethacin-induced elevations in MDA, NF-κB, and caspase-3 levels. These results indicate that astaxanthin exhibits a comparable protective effect to omeprazole, against indomethacin-induced gastric ulceration. This anti-ulcerogenic effect could be mediated through its antioxidant, anti-inflammatory, and anti-apoptotic modulatory activities.
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Affiliation(s)
- Mohamed H Aly
- Pharmacology Department, Faculty of Pharmacy, The British University in Egypt, Cairo, 11837, Egypt.
- Health Research Center of Excellence; Drug Research and Development Group, Faculty of Pharmacy, The British University in Egypt, Cairo, 11837, Egypt.
| | - Aya K Said
- Pharmacology Department, Faculty of Pharmacy, The British University in Egypt, Cairo, 11837, Egypt
- Health Research Center of Excellence; Drug Research and Development Group, Faculty of Pharmacy, The British University in Egypt, Cairo, 11837, Egypt
| | - Aya M Farghaly
- Faculty of Pharmacy, The British University in Egypt, Cairo, 11837, Egypt
| | - Dalia A Eldaly
- Faculty of Pharmacy, The British University in Egypt, Cairo, 11837, Egypt
| | - Dina S Ahmed
- Faculty of Pharmacy, The British University in Egypt, Cairo, 11837, Egypt
| | - Maram H Gomaa
- Faculty of Pharmacy, The British University in Egypt, Cairo, 11837, Egypt
| | - Nazih H Elgebaly
- Faculty of Pharmacy, The British University in Egypt, Cairo, 11837, Egypt
| | - Omar Sameh
- Faculty of Pharmacy, The British University in Egypt, Cairo, 11837, Egypt
| | - Salma K Elahwany
- Faculty of Pharmacy, The British University in Egypt, Cairo, 11837, Egypt
| | - Tasneem T Ebrahem
- Faculty of Pharmacy, The British University in Egypt, Cairo, 11837, Egypt
| | - Youssif Sameh
- Faculty of Pharmacy, The British University in Egypt, Cairo, 11837, Egypt
| | - Maha E Wally
- Pharmacology Department, Faculty of Pharmacy, The British University in Egypt, Cairo, 11837, Egypt.
- Health Research Center of Excellence; Drug Research and Development Group, Faculty of Pharmacy, The British University in Egypt, Cairo, 11837, Egypt.
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13
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Darkazally AZ, Alnour A, Homsi S. Troxerutin effect on gastric ulcers induced by ketorolac in rats: Relation with oxidative stress. Heliyon 2024; 10:e38893. [PMID: 39435065 PMCID: PMC11492593 DOI: 10.1016/j.heliyon.2024.e38893] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Revised: 09/03/2024] [Accepted: 10/01/2024] [Indexed: 10/23/2024] Open
Abstract
Gastric ulcers are an essential side effect associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs). Free radicals are one of the important mechanisms contributing to the development of gastric ulcers caused by NSAIDs. This prompted us to choose troxerutin, which has antioxidant and anti-inflammatory effects, especially with a lack of studies investigating the preventive effect of troxerutin on gastric ulcers. Twenty-nine rats were divided into five groups: A Vehicle group, a Keto group (30 mg/kg of ketorolac), and two troxerutin groups (150 mg/kg or 200 mg/kg of troxerutin, respectively). A Miso group was used as a reference with (100 μg/kg of misoprostol). Troxerutin and misoprostol were administered orally 1 h before ketorolac. The ulcer index was determined considering the numbers and severity of ulcerations. Gastric tissue inflammation was evaluation microscopically. Both thiobarbituric acid reactive substance levels and catalase activity were measured as markers of oxidative stress in gastric tissue. Our data showed an improvement in ulcer indices with troxerutin and misoprostol compared with ketorolac, with improvement in gastric inflammation observed with misoprostol but not with troxerutin. These results were accompanied by a reduction in gastric oxidative stress induced by ketorolac with both troxerutin and misoprostol. This study highlights, for the first time, the antioxidant effect of troxerutin on gastric ulcers. This effect may contribute to the good prevention of ketorolac-induced gastric ulcers.
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Affiliation(s)
| | - Amirah Alnour
- Department of Histology and Pathological Anatomy, Faculty of Dentistry, Damascus University, Damascus, Syria
| | - Shadi Homsi
- Department of Pharmacology, Faculty of Pharmacy, Damascus University, Damascus, Syria
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14
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Rizzo MG, Zammuto V, Spanò A, Gugliandolo C, Calabrese G, Guglielmino S. Anti-inflammatory effects in LPS-induced macrophages and antibiofilm activity of the mannose-rich exopolysaccharide produced by Bacillus licheniformis B3-15. Heliyon 2024; 10:e38367. [PMID: 39398053 PMCID: PMC11470526 DOI: 10.1016/j.heliyon.2024.e38367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Revised: 09/22/2024] [Accepted: 09/23/2024] [Indexed: 10/15/2024] Open
Abstract
The mannose-rich exopolysaccharide EPS B3-15, produced by the thermophilic Bacillus licheniformis B3-15, was previously reported to possess promising potentialities as antiviral and immunomodulatory agent, and in preventing the adhesion of Pseudomonas aeruginosa and Staphylococcus aureus. In this study, EPS B3-15 was evaluated for its anti-inflammatory activity in LPS-induced macrophages and the ability to contrast the adhesion of Klebsiella pneumoniae and Streptococcus pneumoniae as pathogenic bacteria of the respiratory tract. Without affecting the macrophages viability, the EPS at low concentration (300 μg/mL) significantly downregulated the gene expression of iNOS and the consequent NO generation, and it also decreased the production of pro-inflammatory cytokines. Moreover, the EPS reduced the adhesion of Str. pneumoniae (47 %) more efficiently than K. pneumoniae (38 %), due to its ability to modify the abiotic surfaces properties and alter the charges of bacterial-cell surface of Gram-positive more than Gram-negative. As able to reduce the inflammatory responses in macrophage cells and simultaneously prevent biofilm-related to the respiratory tract infections, EPS B3-15 could have potential use as nasal spray with anti-inflammatory action and surface-coating agent for medical devices.
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Affiliation(s)
| | | | - Antonio Spanò
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d’Alcontres, 31, 98166, Messina, Italy
| | - Concetta Gugliandolo
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d’Alcontres, 31, 98166, Messina, Italy
| | - Giovanna Calabrese
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d’Alcontres, 31, 98166, Messina, Italy
| | - Salvatore Guglielmino
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d’Alcontres, 31, 98166, Messina, Italy
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15
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Shaik RA. Parthenolide alleviates indomethacin-induced gastric ulcer in rats via antioxidant, anti-inflammatory, and antiapoptotic activities. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2024; 397:7683-7695. [PMID: 38703207 DOI: 10.1007/s00210-024-03110-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Accepted: 04/18/2024] [Indexed: 05/06/2024]
Abstract
Parthenolide (PTL) is a sesquiterpene lactone that occurs naturally. It demonstrates a variety of beneficial effects, such as antioxidant, anti-inflammatory, and antiapoptotic properties. The study investigated the potential protective impact of PTL on indomethacin (INDO) induced stomach ulcers in rats. The rats were classified into 5 distinct categories. Group 1 served as the "control" group. Rats in the second group received a single oral dosage of INDO (50 mg kg-1). Rats in Groups three and four received 20 and 40 mg kg-1 oral PTL 1 h before INDO. Omeprazole (30 mg kg-1) was given orally to Group 5 rats 1 h before INDO. Pretreatment with PTL increased stomach pH and decreased gastric volume as well as reduced the morphological and histological changes induced by INDO. Analysis of probable pathways showed that pre-treatment with PTL successfully reduced oxidative, inflammatory, and apoptotic consequences caused by INDO. The ingestion of PTL leads to a notable increase in the levels of glutathione reduced (GSH) and the activities of superoxide dismutase (SOD) and catalase (CAT). Furthermore, PTL decreased the concentration of malondialdehyde (MDA). In contrast, it was shown that PTL increased both cyclooxygenase-1 (COX-1) and prostaglandin E2 (PGE2). PTL shows a significant decrease in the expression of interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), inducible nitric oxide synthase (iNOS), and nuclear factor kappa B (NF-κB). PTL therapy resulted in a decrease in Bcl-2-associated X protein (Bax) levels and an increase in B-cell lymphoma 2 (Bcl2) levels. In conclusion, PTL offers gastroprotection by its antioxidant, anti-inflammatory, and anti-apoptotic qualities.
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Affiliation(s)
- Rasheed A Shaik
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.
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16
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Al Shboul S, Maloul O, Al-Trad H, Maloul Y, AlHarahsheh W, Mosallam D, Al-Sarayreh S, AlRashaydah R, AlSarayreh A, Khasawneh AI, Saleh T. Self-Reported Gastrointestinal Symptoms Associated with NSAIDs and Caffeine Consumption in a Jordanian Subpopulation. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:1519. [PMID: 39336561 PMCID: PMC11433810 DOI: 10.3390/medicina60091519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Revised: 09/14/2024] [Accepted: 09/16/2024] [Indexed: 09/30/2024]
Abstract
Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) and caffeine-containing beverages are widely consumed but their impact on gastrointestinal (GI) health requires further investigation. This cross-sectional study investigated the relationship between NSAIDs use, caffeinated drink consumption, and the prevalence of self-reported GI symptoms in a Jordanian subpopulation. Methods: An online survey was administered to 400 Jordanian individuals aged 18-65 years. Data on sociodemographics, NSAIDs use, caffeine consumption, peptic ulcer disease (PUD) history, and GI symptoms were collected. Contingency tables were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between exposures and outcomes. Results: The prevalence of self-reported PUD-related GI symptoms was 6.0%. NSAID users had higher odds of PUD (OR = 2.431) and related GI symptoms, including abdominal pain (OR = 4.688, p < 0.001) and discomfort (OR = 8.068, p < 0.001). Caffeine consumption was associated with self-reported burning stomach pain (OR = 14.104, p < 0.001), fullness (OR = 8.304, p = 0.010), and bloating (OR = 8.304, p = 0.010). Coffee, tea, soft drinks, and energy drinks were associated with increased odds of various GI symptoms (ORs 2.018-12.715, p < 0.05). Conclusions: NSAIDs use and caffeine consumption were independently associated with the increased prevalence of self-reported PUD and related GI symptoms. Despite the lack of adjustment for necessary confounders, our findings highlight the importance of considering the potential GI effects of NSAIDs and caffeine. Public health strategies promoting their safe use may help reduce the burden of GI disorders.
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Affiliation(s)
- Sofian Al Shboul
- Department of Pharmacology and Public Health, Faculty of Medicine, The Hashemite University, Zarqa 13133, Jordan
| | - Omar Maloul
- Department of Pharmacology and Public Health, Faculty of Medicine, The Hashemite University, Zarqa 13133, Jordan
| | - Hamza Al-Trad
- Department of Pharmacology and Public Health, Faculty of Medicine, The Hashemite University, Zarqa 13133, Jordan
| | - Yazan Maloul
- Department of Pharmacology and Public Health, Faculty of Medicine, The Hashemite University, Zarqa 13133, Jordan
| | - Wa'ed AlHarahsheh
- Department of Pharmacology and Public Health, Faculty of Medicine, The Hashemite University, Zarqa 13133, Jordan
| | - Doa'a Mosallam
- Department of Pharmacology and Public Health, Faculty of Medicine, The Hashemite University, Zarqa 13133, Jordan
| | - Sondos Al-Sarayreh
- Department of Pharmacology and Public Health, Faculty of Medicine, The Hashemite University, Zarqa 13133, Jordan
| | - Rania AlRashaydah
- Department of Pharmacology and Public Health, Faculty of Medicine, The Hashemite University, Zarqa 13133, Jordan
| | - Aya AlSarayreh
- Department of Pharmacology and Public Health, Faculty of Medicine, The Hashemite University, Zarqa 13133, Jordan
| | - Ashraf I Khasawneh
- Department of Microbiology, Pathology, and Forensic Medicine, Faculty of Medicine, The Hashemite University, Zarqa 13133, Jordan
- Department of Laboratory Medicine, National Institutes of Health Clinical Center, Bethesda, MD 20892, USA
| | - Tareq Saleh
- Department of Pharmacology and Public Health, Faculty of Medicine, The Hashemite University, Zarqa 13133, Jordan
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Ojo C, Orji C, Anifalaje O, Garg G, Anto M, Kelly M. Retrospective study on pain management pathway for patients with suspected renal/ ureteric colic in a U.K. accidents and emergency department: A quality improvement project. F1000Res 2024; 13:1052. [PMID: 40144463 PMCID: PMC11937778 DOI: 10.12688/f1000research.152325.1] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/28/2024] [Indexed: 03/28/2025] Open
Abstract
Background In acute settings around the globe, renal/ureteric colic remains one of the most common diagnoses for patients presenting with loin-to-groin pain. Even though management spans from medical expulsive therapies to surgical options, pain as a significant component of a patient's presentation must be dealt with quickly, decisively, and safely, as it can be excruciating and its effects on overall health are dire. This study aimed to explore compliance with the National Institute for Health and Care Excellence (NICE) guidelines for pain management in patients with suspected renal/ureteric colic. It includes the use of nonsteroidal anti-inflammatory drugs (NSAIDs), intravenous paracetamol, and opioids as first-, second-, and third-line analgesics, respectively, and does not offer antispasmodics. In the event of deviations from the standard, the aim was to put in corrective measures, followed by re-exploration of compliance with patient care. Methods This study involved a single healthcare facility with the study type being retrospective before interventions and prospective after interventions. In the first cycle, we retrieved and analysed 78 patients records whom had been suspected to have renal/ureteric colic between July and September 2022. The inclusion criteria were documented complaints of "flank/loin-to-groin pain" and diagnosis prior to performing diagnostic tests. We surveyed the first-, second-, and third-line painkillers issued, and whether an antispasmodic was given. We collected and entered data into a Microsoft Excel file and correlated it with NICE standards. Having found deviations from the standard, we conducted interventions, allowed time for clinicians to adapt, and re-explored compliance using patient case records [n=58] between February and May 2023. Results In the 1 st cycle, 78 patients were suspected of having renal/ureteric colic. M: F = 1.2:1. Non-contrast computerized tomography of the kidney ureters and bladder (NC-CTKUB) confirmed 87% of patients with stones and 3% had no stones. NC-CTKUB was not performed in 9% of patients because they were young, and urinalysis showed no microscopic hematuria. One patient had discharged against medical advise before the NC-CTKUB was performed. Compliance with the NICE pain management guidelines for suspected renal/ureteric colic was full in 23% of cases but unsatisfactory in 78% of cases. In the 2 nd cycle, M: F = 1.5:1, NC-CTKUB was not re-audited, as the first cycle study yielded excellent results, and our action plan resulted in an NICE pain management compliance rate of 56%. Although our interventions resulted in improvements of more than twice the initial results, work still needs to be performed. Conclusion Clinicians' ability to correctly diagnose renal/ureteric colic is remarkable. However, the pain management compliance rate indicates room for improvement. This may be due to the limited awareness of the NICE guideline or the fact that the clinical team has an affinity for certain analgesics compared to others. We propose the need to consider select variables to existing standard guidelines to enhance compliance for improved patient care.
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Affiliation(s)
- Charles Ojo
- Emergency Department, Pilgrim Hospital, United Lincolnshire Hospitals NHS Trust, Boston, Lincolnshire, PE21 9QS, UK
| | - Chijioke Orji
- Trauma and Orthopaedics, Royal Cornwall Hospital, Truro, England, TR1 3LJ, UK
| | - Olorungbami Anifalaje
- Emergency Department, Dumfies and Galloway Royal Infirmary, Cargenbridge, Dumfries, DG2 8RX, UK
| | - Gourav Garg
- Emergency Department, King's Mill Hospital, Sherwood Forest Hospitals NHS Foundation Trust, Sutton-in-Ashfield, Nottinghamshire, NG17 4JL, UK
| | - Mariette Anto
- Emergency Department, King's Mill Hospital, Sherwood Forest Hospitals NHS Foundation Trust, Sutton-in-Ashfield, Nottinghamshire, NG17 4JL, UK
| | - Megan Kelly
- Emergency Department, Pilgrim Hospital, United Lincolnshire Hospitals NHS Trust, Boston, Lincolnshire, PE21 9QS, UK
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18
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Joshi DC, Joshi N, Kumar A, Maheshwari S. Recent Advances in Molecular Pathways and Therapeutic Implications for Peptic Ulcer Management: A Comprehensive Review. Horm Metab Res 2024; 56:615-624. [PMID: 38467155 DOI: 10.1055/a-2256-6592] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/13/2024]
Abstract
Peptic ulcers, recognized for their erosive impact on the gastrointestinal mucosa, present a considerable challenge in gastroenterology. Epidemiological insights underscore the global prevalence of peptic ulcers, affecting 5-10+% of individuals, with a yearly incidence of 0.3 to 1.9 cases per thousand. Recent decades have witnessed a decline in complications, attributed to improved diagnostics and therapeutic advancements. The review deepens into H. pylori-associated and NSAID-induced ulcers, emphasizing their distinct prevalence in developing and industrialized nations, respectively. Despite advancements, managing peptic ulcers remains challenging, notably in H. pylori-infected individuals facing recurrence and the rise of antibiotic resistance. The pathophysiology unravels the delicate balance between protective and destructive factors, including the intricate molecular mechanisms involving inflammatory mediators such as TNF-α, ILs, and prostaglandins. Genetic and ethnic factors, rare contributors, and recent molecular insights further enhance our understanding of peptic ulcer development. Diagnostic approaches are pivotal, with upper gastrointestinal endoscopy standing as the gold standard. Current treatment strategies focus on H. pylori eradication, NSAID discontinuation, and proton pump inhibitors. Surgical options become imperative for refractory cases, emphasizing a comprehensive approach. Advances include tailored H. pylori regimens, the emergence of vonoprazan, and ongoing vaccine development. Challenges persist, primarily in antibiotic resistance, side effects of acid suppressants, and translating natural compounds into standardized therapies. Promising avenues include the potential H. pylori vaccine and the exploration of natural compounds, with monoterpenes showing therapeutic promise. This review serves as a compass, guiding healthcare professionals, researchers, and policymakers through the intricate landscape of peptic ulcer management.
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Affiliation(s)
- Deepak Chandra Joshi
- Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Ajmer, India
| | - Nirmal Joshi
- Department of Pharmacology, Amrapali Institute of Pharmacy and Sciences, Haldwani, India
| | - Ajeet Kumar
- Faculty of Pharmaceutical Sciences, Rama University, Kanpur, India
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19
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Maity R, Dhali A, Biswas J. Importance of risk assessment, endoscopic hemostasis, and recent advancements in the management of acute non-variceal upper gastrointestinal bleeding. World J Clin Cases 2024; 12:5462-5467. [PMID: 39188600 PMCID: PMC11269988 DOI: 10.12998/wjcc.v12.i24.5462] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2024] [Revised: 04/20/2024] [Accepted: 05/17/2024] [Indexed: 07/11/2024] Open
Abstract
Acute non-variceal upper gastrointestinal bleeding (ANVUGIB) is a common medical emergency in clinical practice. While the incidence has significantly reduced, the mortality rates have not undergone a similar reduction in the last few decades, thus presenting a significant challenge. This editorial outlines the key causes and risk factors of ANVUGIB and explores the current standards and recent updates in risk assessment scoring systems for predicting mortality and endoscopic treatments for achieving hemostasis. Since ANUVGIB predominantly affects the elderly population, the impact of comorbidities may be responsible for the poor outcomes. A thorough drug history is important due to the increasing use of antiplatelet agents and anticoagulants in the elderly. Early risk stratification plays a crucial role in deciding the line of management and predicting mortality. Emerging scoring systems such as the ABC (age, blood tests, co-morbidities) score show promise in predicting mortality and guiding clinical decisions. While conventional endoscopic therapies remain cornerstone approaches, novel techniques like hemostatic powders and over-the-scope clips offer promising alternatives, particularly in cases refractory to traditional modalities. By integrating validated scoring systems and leveraging novel therapeutic modalities, clinicians can enhance patient care and mitigate the substantial morbidity and mortality associated with ANVUGIB.
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Affiliation(s)
- Rick Maity
- General Medicine, Institute of Post Graduate Medical Education and Research, Kolkata 700020, India
| | - Arkadeep Dhali
- Department of Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, Northern General Hospital, Sheffield S5 7AU, United Kingdom
- School of Medicine and Population Health, University of Sheffield, Sheffield S102HQ, United Kingdom
| | - Jyotirmoy Biswas
- General Medicine, College of Medicine and Sagore Dutta Hospital, Kolkata 700058, India
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Tallmadge M, MacBeth M, Palatnik A. New Onset of Symptomatic Peptic Ulcer Disease Postpartum Secondary to Nonsteroidal Anti-Inflammatory Drug Use. Case Rep Obstet Gynecol 2024; 2024:6422824. [PMID: 38962291 PMCID: PMC11221993 DOI: 10.1155/2024/6422824] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2023] [Revised: 03/25/2024] [Accepted: 05/06/2024] [Indexed: 07/05/2024] Open
Abstract
The use of nonsteroidal anti-inflammatory drug (NSAID) medications is a risk factor for peptic ulcer disease (PUD). PUD in the postpartum period is rare, despite the common use of NSAIDs. A G1P0 presented 6 days postcesarean section with fatigue, lightheadedness, melenic stools, and a hemoglobin of 5.4 g/dL after using NSAIDs and acetaminophen for postoperative pain control. An esophagogastroduodenoscopy (EGD) was performed for a suspected upper gastrointestinal bleed and found one gastric and one duodenal ulcer. Though typically used for a short course in the postpartum period, NSAIDs remain a predisposing risk factor for PUD postpartum, and patients and providers must be aware of this risk.
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Affiliation(s)
- Maggie Tallmadge
- Department of Obstetrics and GynecologyMedical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Margaret MacBeth
- Department of Obstetrics and GynecologyMedical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Anna Palatnik
- Department of Obstetrics and GynecologyMedical College of Wisconsin, Milwaukee, Wisconsin, USA
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Elgohary MK, Elkotamy MS, Abdelrahman Alkabbani M, Abdel-Aziz HA. Fenamates and ibuprofen as foundational components in the synthesis of innovative, targeted COX-2 anti-inflammatory drugs, undergoing thorough biopharmacological assessments and in-silico computational studies. Bioorg Chem 2024; 147:107393. [PMID: 38691908 DOI: 10.1016/j.bioorg.2024.107393] [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: 03/20/2024] [Revised: 04/13/2024] [Accepted: 04/23/2024] [Indexed: 05/03/2024]
Abstract
Cyclooxygenase-2 plays a vital role in inflammation by catalyzing arachidonic acid conversion toward prostaglandins, making it a prime therapeutic objective. Selective COX-2 inhibitors represent significant progress in anti-inflammatory therapy, offering improved efficacy and fewer side effects. This study describes the synthesis of novel anti-inflammatory compounds from established pharmaceutically marketed agents like fenamates III-V and ibuprofen VI. Through rigorous in vitro testing, compounds 7b-c, and 12a-b demonstrated substantial in vitro selective inhibition, with IC50 values of 0.07 to 0.09 μM, indicating potent pharmacological activity. In vivo assessment, particularly focusing on compound 7c, revealed significant anti-inflammatory effects. Markedly, it demonstrated the highest inhibition of paw thickness (58.62 %) at the 5-hr mark compared to the carrageenan group, indicating its potency in mitigating inflammation. Furthermore, it exhibited a rapid onset of action, with a 54.88 % inhibition observed at the 1-hr mark. Subsequent comprehensive evaluations encompassing analgesic efficacy, histological characteristics, and toxicological properties indicated that compound 7c did not induce gastric ulcers, in contrast to the ulcerogenic tendency associated with mefenamic acid. Moreover, compound 7c underwent additional investigations through in silico methodologies such as molecular modelling, field alignment, and density functional theory. These analyses underscored the therapeutic potential and safety profile of this novel compound, warranting further exploration and development in the realm of pharmaceutical research.
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Affiliation(s)
- Mohamed K Elgohary
- Pharmaceutical Chemistry Department, Faculty of Pharmacy, Egyptian-Russian University, Badr City Cairo 11829, Egypt.
| | - Mahmoud S Elkotamy
- Pharmaceutical Chemistry Department, Faculty of Pharmacy, Egyptian-Russian University, Badr City Cairo 11829, Egypt
| | - Mahmoud Abdelrahman Alkabbani
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Egyptian-Russian University, Badr City, Cairo 11829, Egypt
| | - Hatem A Abdel-Aziz
- Applied Organic Chemistry Department, National Research Center, Dokki, Cairo 12622, Egypt
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22
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Wu T, Zhang H, Jin Y, Zhang M, Zhao Q, Li H, Wang S, Lu Y, Chen S, Du H, Liu T, Guo W, Liu W. The active components and potential mechanisms of Wuji Wan in the treatment of ethanol-induced gastric ulcer: An integrated metabolomics, network pharmacology and experimental validation. JOURNAL OF ETHNOPHARMACOLOGY 2024; 326:117901. [PMID: 38341112 DOI: 10.1016/j.jep.2024.117901] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Revised: 02/04/2024] [Accepted: 02/08/2024] [Indexed: 02/12/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Wuji Wan (WJW) is a traditional Chinese medicine formula that can be found in the "Prescriptions of Taiping Benevolent Dispensary" that has been employed in treating gastric discomfort, burning epigastric pain, and gastric reflux for hundreds of years and has shown promise for treating gastric ulcers (GUs). However, the active components and mechanism of action against GUs remain unclear. AIM OF THE STUDY The aim of this study was to explore the active components of WJW and elucidate the underlying mechanism involved in treating GUs. MATERIALS AND METHODS Initially, cell viability was measured by a cell counting kit 8 (CCK-8) assay to evaluate the efficacy of WJW-containing serum in vitro. The gastric ulcer index, ulcer inhibition rate, hematoxylin and staining (H&E), and periodic acid-Schiff (PAS) staining were used to evaluate the therapeutic effect of WJW in vivo. Subsequently, the levels of inflammatory factors and oxidative stress factors were determined using an enzyme-linked immunosorbent assays (ELISA) on in vitro and in vivo samples. Additionally, UPLC-Q Exactive Plus Orbitrap HRMS was used to analyze the components that were absorbed into the blood of WJW and its metabolites. Network pharmacology and metabolomics were subsequently used to identify the targets and pathways. Real-time quantitative PCR (RT‒qPCR) and Western blotting were used to verify the mRNA and protein levels of the key targets and pathways. Finally, the active components were identified by molecular docking to verify the binding stability of the components and key targets. RESULTS WJW-containing serum ameliorated ethanol-induced damage in GES-1 cells and promoted cell healing. WJW-containing serum reduced IL-6, TNF-α, MDA, and LDH levels while increasing IL-10, SOD, and T-AOC levels in the cells. Moreover, WJW treatment resulted in decreased IL-6, TNF-α, and MDA levels and increased IL-10, SOD, PGE2, and NO levels in GUs rats. In addition, eight components of WJW were absorbed into the blood. The network pharmacology results revealed 192 common targets for blood entry components and GUs, and KEGG analysis revealed that apoptosis signaling pathways were the main pathways involved in WJW activity against GUs. Metabolomic screening was used to identify 13 differential metabolites. There were 23 common targets for blood entry components, GUs, and differential metabolites, with the key targets TNF (TNF-α), AKT1, PTGS2 (COX2) and MAPK1. WJW significantly inhibited the expression of Bax, Caspase-9, Caspase-3, cleaved Caspase-9, cleaved Caspase-3, TNF-α, COX2, and p-p44/42 MAPK while promoting the expression of Bcl-2 and p-AKT1. Molecular docking revealed that the active components of WJW for the treatment of GUs are berberine, palmatine, coptisine, evodiamine, rutaecarpine, evocarpine, and paeoniflorin. CONCLUSIONS WJW treatment reduces inflammation and oxidative stress injury and inhibits apoptosis signaling pathways. The main active components are berberine, palmatine, coptisine, evodiamine, rutaecarpine, evocarpine, and paeoniflorin. In this paper, we provide a new strategy for exploring the active components of traditional Chinese medicine formulas for the treatment of diseases based on target mechanisms.
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Affiliation(s)
- Tiantai Wu
- School of Basic Medical Sciences, Guizhou Medical University, Guiyang, 550004, China
| | - Huan Zhang
- School of Pharmacy, Guizhou Medical University, Guiyang, 550004, China
| | - Yang Jin
- School of Pharmacy, Guizhou Medical University, Guiyang, 550004, China; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, 550004, China
| | - Ming Zhang
- School of Basic Medical Sciences, Guizhou Medical University, Guiyang, 550004, China; Natural Products Research Center of Guizhou Province, Guiyang, 550014, China
| | - Qing Zhao
- School of Pharmacy, Guizhou Medical University, Guiyang, 550004, China
| | - Herong Li
- School of Pharmacy, Guizhou Medical University, Guiyang, 550004, China
| | - Shouli Wang
- School of Pharmacy, Guizhou Medical University, Guiyang, 550004, China
| | - Yuan Lu
- State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, 550004, China
| | - Shuaishuai Chen
- State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, 550004, China
| | - Huakang Du
- School of Pharmacy, Guizhou Medical University, Guiyang, 550004, China
| | - Ting Liu
- State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, 550004, China
| | - Weiyu Guo
- School of Pharmacy, Guizhou Medical University, Guiyang, 550004, China
| | - Wen Liu
- School of Basic Medical Sciences, Guizhou Medical University, Guiyang, 550004, China; School of Pharmacy, Guizhou Medical University, Guiyang, 550004, China.
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Rosa Júnior IA, Almeida DDS, Napolitano HB, Peixoto JDC, Rosseto LP, Hungria Pinto EM, Dias LD, Fajemiroye JO, Costa EA, Vieira RP, Martins JLR. Evaluation of Gastroprotective Activity of the Methanolic Extract of Justicia pectoralis Jacq. (Acanthaceae). Nutrients 2024; 16:1430. [PMID: 38794668 PMCID: PMC11123913 DOI: 10.3390/nu16101430] [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: 01/25/2024] [Revised: 04/19/2024] [Accepted: 04/25/2024] [Indexed: 05/26/2024] Open
Abstract
INTRODUCTION Justicia pectoralis Jacq. is traditionally applied in folk medicine in Brazil and in several Latin American countries. The leaves are used in tea form, especially in the treatment of respiratory disorders, acting as an expectorant. It also has activity in gastrointestinal disorders, and it is anti-inflammatory, antioxidant, sedative, and estrogenic, among others. AIMS To investigate the gastroprotective activity of the methanol extract of the leaves of Justicia pectoralis Jacq. (MEJP) in different experimental models of gastric ulcers. MATERIALS AND METHODS The adult leaves of Justicia pectoralis Jacq. were collected and cultivated in beds, with an approximate spacing of 40 × 40 cm, organic fertilization, irrigation with potable water and without shelter from light. The MEJP was prepared from the dried and pulverized leaves and concentrated under reduced pressure in a rotary evaporator. For the experimental model of gastric ulcer, Swiss male albino mice were used. The inputs used in the experiment were MEJP at three different concentrations (250, 500 and 1000 mg/kg p.o.), cimetidine (50 mg/kg p.o.), indomethacin (50 mg/kg s.c.) and vehicle (10 mL/kg p.o.). RESULTS MEJP (250, 500 and 1000 mg/kg p.o.) demonstrated gastroprotective activity, with levels of protection of 45.65%, 44.80% and 40.22%, respectively, compared to the control (vehicle). Compared with cimetidine (48.29%), MEJP showed similar gastroprotective activity. CONCLUSIONS This study demonstrated the gastroprotective activity of MEJP and contributes to validate the traditional use the species for gastric disorders and provides a pharmacological basis for its clinical potential.
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Affiliation(s)
- Ismael Aureliano Rosa Júnior
- Postgraduate Program in Pharmaceutical Sciences, Pharmacology and Therapeutics, Evangelical University of Goiás—Unievangélica, University Avenue Km 3,5, Anápolis 75083-515, GO, Brazil; (I.A.R.J.); (H.B.N.); (J.d.C.P.); (L.P.R.); (E.M.H.P.); (L.D.D.); (J.O.F.); (R.P.V.)
- Instituto de Ciência, Tecnologia e Qualidade—ICTQ, Anápolis 75023-085, GO, Brazil
| | - Dionys de Souza Almeida
- Institute of Biological Sciences, Department of Pharmacology, Federal University of Goiás, Campus Samambaia, Campus Street, Goiânia 74001-97, GO, Brazil; (D.d.S.A.); (E.A.C.)
| | - Hamilton Barbosa Napolitano
- Postgraduate Program in Pharmaceutical Sciences, Pharmacology and Therapeutics, Evangelical University of Goiás—Unievangélica, University Avenue Km 3,5, Anápolis 75083-515, GO, Brazil; (I.A.R.J.); (H.B.N.); (J.d.C.P.); (L.P.R.); (E.M.H.P.); (L.D.D.); (J.O.F.); (R.P.V.)
- Campus Central, State University of Goiás, Anápolis 75132-400, GO, Brazil
| | - Josana de Castro Peixoto
- Postgraduate Program in Pharmaceutical Sciences, Pharmacology and Therapeutics, Evangelical University of Goiás—Unievangélica, University Avenue Km 3,5, Anápolis 75083-515, GO, Brazil; (I.A.R.J.); (H.B.N.); (J.d.C.P.); (L.P.R.); (E.M.H.P.); (L.D.D.); (J.O.F.); (R.P.V.)
- Campus Central, State University of Goiás, Anápolis 75132-400, GO, Brazil
| | - Lucimar Pinheiro Rosseto
- Postgraduate Program in Pharmaceutical Sciences, Pharmacology and Therapeutics, Evangelical University of Goiás—Unievangélica, University Avenue Km 3,5, Anápolis 75083-515, GO, Brazil; (I.A.R.J.); (H.B.N.); (J.d.C.P.); (L.P.R.); (E.M.H.P.); (L.D.D.); (J.O.F.); (R.P.V.)
| | - Emerith Mayra Hungria Pinto
- Postgraduate Program in Pharmaceutical Sciences, Pharmacology and Therapeutics, Evangelical University of Goiás—Unievangélica, University Avenue Km 3,5, Anápolis 75083-515, GO, Brazil; (I.A.R.J.); (H.B.N.); (J.d.C.P.); (L.P.R.); (E.M.H.P.); (L.D.D.); (J.O.F.); (R.P.V.)
- Campus Central, State University of Goiás, Anápolis 75132-400, GO, Brazil
| | - Lucas Danilo Dias
- Postgraduate Program in Pharmaceutical Sciences, Pharmacology and Therapeutics, Evangelical University of Goiás—Unievangélica, University Avenue Km 3,5, Anápolis 75083-515, GO, Brazil; (I.A.R.J.); (H.B.N.); (J.d.C.P.); (L.P.R.); (E.M.H.P.); (L.D.D.); (J.O.F.); (R.P.V.)
| | - James Oluwagbamigbe Fajemiroye
- Postgraduate Program in Pharmaceutical Sciences, Pharmacology and Therapeutics, Evangelical University of Goiás—Unievangélica, University Avenue Km 3,5, Anápolis 75083-515, GO, Brazil; (I.A.R.J.); (H.B.N.); (J.d.C.P.); (L.P.R.); (E.M.H.P.); (L.D.D.); (J.O.F.); (R.P.V.)
- Institute of Biological Sciences, Department of Pharmacology, Federal University of Goiás, Campus Samambaia, Campus Street, Goiânia 74001-97, GO, Brazil; (D.d.S.A.); (E.A.C.)
| | - Elson Alves Costa
- Institute of Biological Sciences, Department of Pharmacology, Federal University of Goiás, Campus Samambaia, Campus Street, Goiânia 74001-97, GO, Brazil; (D.d.S.A.); (E.A.C.)
| | - Rodolfo P. Vieira
- Postgraduate Program in Pharmaceutical Sciences, Pharmacology and Therapeutics, Evangelical University of Goiás—Unievangélica, University Avenue Km 3,5, Anápolis 75083-515, GO, Brazil; (I.A.R.J.); (H.B.N.); (J.d.C.P.); (L.P.R.); (E.M.H.P.); (L.D.D.); (J.O.F.); (R.P.V.)
- Postgraduate Program in Human Movement and Rehabilitation, Evangelical University of Goiás—Unievangélica, University Avenue Km 3,5, Anápolis 75083-515, GO, Brazil
| | - José Luis Rodrigues Martins
- Postgraduate Program in Pharmaceutical Sciences, Pharmacology and Therapeutics, Evangelical University of Goiás—Unievangélica, University Avenue Km 3,5, Anápolis 75083-515, GO, Brazil; (I.A.R.J.); (H.B.N.); (J.d.C.P.); (L.P.R.); (E.M.H.P.); (L.D.D.); (J.O.F.); (R.P.V.)
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24
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Ali G, Deeba F, Rashid U, Ullah A, Ullah H, Khan IA, Khan SI, Badshah A, Khan MA, Ayaz M, Daglia M. In vivo effects of a selected thiourea derivative 1-(2-chlorobenzoyl)-3-(2,3-dichlorophenyl) against nociception, inflammation and gastric ulcerogenicity: Biochemical, histopathological and in silico approaches. Biomed Pharmacother 2024; 174:116544. [PMID: 38599058 DOI: 10.1016/j.biopha.2024.116544] [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: 03/07/2024] [Revised: 04/03/2024] [Accepted: 04/04/2024] [Indexed: 04/12/2024] Open
Abstract
The current study was designed to investigate the potential of a synthetic therapeutic agent for better management of pain and inflammation, exhibiting minimal to non-existent ulcerogenic effects. The effect of 1-(2-chlorobenzoyl)-3-(2,3-dichlorophenyl) thiourea was assessed through model systems of nociception and anti-inflammatory activities in mice. In addition, the ulcerogenic potential was evaluated in rats using the NSAID-induced pyloric ligation model, followed by histopathological and biochemical analysis. The test was conducted on eight groups of albino rats, comprising of group I (normal saline), groups II and III (aspirin® at doses of 100 mg/kg and 150 mg/kg, respectively), groups IV and V (indomethacin at doses of 100 mg/kg and 150 mg/kg, respectively), and groups VI, VII, and VIII (lead-compound at 15 mg/kg, 30 mg/kg and 45 mg/kg doses, respectively). Furthermore, molecular docking analyses were performed to predict potential molecular target site interactions. The results showed that the lead-compound, administered at doses of 15, 30, and 45 mg/kg, yielded significant reductions in chemically and thermally induced nociceptive pain, aligning with the levels observed for aspirin® and tramadol. The compound also effectively suppressed inflammatory response in the carrageenan-induced paw edema model. As for the ulcerogenic effects, the compound groups displayed no considerable alterations compared to the aspirin® and indomethacin groups, which displayed substantial increases in ulcer scores, total acidity, free acidity, and gastric juice volume, and a decrease in gastric juice pH. In conclusion, these findings suggest that our test compound exhibits potent antinociceptive, anti-inflammatory properties and is devoid of ulcerogenic effects.
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Affiliation(s)
- Gowhar Ali
- Department of Pharmacy, University of Peshawar, Peshawar, Pakistan.
| | - Farrah Deeba
- Department of Pharmacy, University of Peshawar, Peshawar, Pakistan
| | - Umer Rashid
- Department of Chemistry, COMSATS University Islamabad, Abbottabad 22060, Pakistan
| | - Aman Ullah
- Department of Pharmacy, University of Peshawar, Peshawar, Pakistan
| | - Hammad Ullah
- Department of Pharmacy, University of Napoli Federico II, Via D. Montesano 49, Naples 80131, Italy.
| | - Inayat Ali Khan
- Department of Chemistry, School of Natural Sciences (SNS), National University of Sciences and Technology (NUST), H-12 Campus, Islamabad 44000, Pakistan
| | - Syed Ishtiaq Khan
- Superintending Chemist, Geological Survey of Pakistan, Sariab Road, Quetta 87550, Pakistan
| | - Amin Badshah
- Department of Chemistry, Quaid-e-Azam University Islamabad, 45320, Pakistan
| | - Muhammad Arif Khan
- Department of Pharmacy, University of Malakand, Dir (L), Chakdara, Khyber Pakhtunkhwa 18000, Pakistan
| | - Muhammad Ayaz
- Department of Pharmacy, University of Malakand, Dir (L), Chakdara, Khyber Pakhtunkhwa 18000, Pakistan.
| | - Maria Daglia
- Department of Pharmacy, University of Napoli Federico II, Via D. Montesano 49, Naples 80131, Italy; International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang 212013, China
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Mansingh PP, Adhikari L, Dhara M. Pharmacognostic standardization and evaluation of antiulcer potential of Olax psittacorum leaf extract. Nat Prod Res 2024:1-9. [PMID: 38462775 DOI: 10.1080/14786419.2024.2327613] [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: 11/27/2023] [Accepted: 02/27/2024] [Indexed: 03/12/2024]
Abstract
The modern medicine has received many plants as a gift from ethnobotany. It is an efficient method of discovering new medicines. The leaves of Olax psittacorum (Lam.) Vahl. were extracted with ethanol, and the phytoconstituents present in the leaf extract were identified using Gas chromatography-mass spectrometric analysis (GC-MS), followed by determination of physico-chemical parameters and anti-ulcer properties. The leaf ethanolic extract (LEE) yield was observed to be 43.2%. The quantitative surface microscopy analysis revealed a stomatal index of 30 and 22 epidermal cells and qualitatively confirms presence of quinone, flavonoid, phenol, carbohydrate, tannin, saponin and absence of alkaloids using various screening techniques. The LEE confirms its anti-ulcer potency by inhibiting ulceration by 58% and 75% respectively, thus proving the hypothesis. These identified parameters may be helpful in developing some botanical standards for the standardisation and identification of O. psittacorum leaves with anti-ulcer properties.
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Affiliation(s)
- Pragyan Parimita Mansingh
- Department of Pharmaceutical Analysis, School of Pharmaceutical Sciences, Siksha 'O' Anusandhan University, Bhubaneswar, Odisha, India
| | - Lopamudra Adhikari
- Department of Pharmaceutical Analysis, School of Pharmaceutical Sciences, Siksha 'O' Anusandhan University, Bhubaneswar, Odisha, India
| | - Moonmun Dhara
- Department of Pharmaceutics, School of Pharmaceutical Sciences, Siksha 'O' Anusandhan University, Bhubaneswar, Odisha, India
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26
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Hansen LØ, Fürst MB, Bjørsum-Meyer T, Schelde-Olesen B, Deding U, Kaalby L. Factors associated with negative colonoscopy in participants with a positive faecal immunochemical test from the Danish Colorectal Cancer Screening Program - a population-based study. Colorectal Dis 2024; 26:476-485. [PMID: 38297072 DOI: 10.1111/codi.16886] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Revised: 12/19/2023] [Accepted: 01/06/2024] [Indexed: 02/02/2024]
Abstract
AIM In the Danish Colorectal Cancer Screening Program (DCCSP), 37% of participants undergoing colonoscopy have a negative result with no obvious findings that can be attributed to a positive faecal immunochemical test (FIT). The aim of this work was to identify predictors for a negative colonoscopy in DCCSP participants with a positive FIT. METHOD We included 73 655 FIT-positive DCCSP participants using the Danish Colorectal Cancer Screening Database and linked their screening results with data from several other national health registers. We stratified participants by all predictors, and compared them using multivariate logistic regression analysis. Results are reported as odds ratios (ORs). RESULTS We found that having a condition linked to gastrointestinal bleeding, for example fissures, haemorrhoids and inflammatory bowel disease, was strongly associated with the probability of having a negative colonoscopy [OR 2.77 (95% CI 2.59, 2.96)]. FIT concentration was inversely related to the probability of a negative colonoscopy, the OR decreased steadily from 0.79 (95% CI 0.75, 0.83) in the 40-59 μg/g group, to 0.44 (95% CI 0.42, 0.46) in the ≥200 μg/g group. Women had a 1.64 (95% CI 1.59, 1.70) times higher probability of a negative colonoscopy than men. CONCLUSION Our findings indicate that baseline conditions linked to gastrointestinal bleeding are an associating factor with having a negative colonoscopy. The same is true for low FIT concentration and female sex. Further studies with similar findings could suggest that an incorporation of these factors into a personalized screening approach by differentiating between diagnostic modalities could improve the process for the participant while alleviating the health care system.
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Affiliation(s)
| | | | - Thomas Bjørsum-Meyer
- Department of Surgery, Odense University Hospital, Odense, Denmark
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Benedicte Schelde-Olesen
- Department of Surgery, Odense University Hospital, Odense, Denmark
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Ulrik Deding
- Department of Surgery, Odense University Hospital, Odense, Denmark
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Lasse Kaalby
- Department of Surgery, Odense University Hospital, Odense, Denmark
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
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27
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Szilcz M, Wastesson JW, Calderón-Larrañaga A, Prieto-Alhambra D, Blotière PO, Maura G, Johnell K. Cholinesterase inhibitors and non-steroidal anti-inflammatory drugs and the risk of peptic ulcers: A self-controlled study. J Am Geriatr Soc 2024; 72:456-466. [PMID: 37905683 DOI: 10.1111/jgs.18647] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2023] [Revised: 09/11/2023] [Accepted: 10/09/2023] [Indexed: 11/02/2023]
Abstract
BACKGROUND Non-steroidal anti-inflammatory drugs (NSAIDs) should be used with caution in adults aged 65 years and older. Their gastrointestinal adverse event risk might be further reinforced when using concomitant cholinesterase inhibitors (ChEIs). We aimed to investigate the association between NSAIDs and ChEI use and the risk of peptic ulcers in adults aged 65 years and older. METHODS Register-based self-controlled case series study including adults ≥65 years with a new prescription of ChEIs and NSAIDs, diagnosed with incident peptic ulcer in Sweden, 2007-2020. We identified persons from the Total Population Register individually linked to several nationwide registers. We estimated the incidence rate ratio (IRR) of peptic ulcer with a conditional Poisson regression model for four mutually exclusive risk periods: use of ChEIs, NSAIDs, and the combination of ChEIs and NSAIDs, compared with the non-treatment in the same individual. Risk periods were identified based on the prescribed daily dose, extracted via a text-parsing algorithm, and a 30-day grace period. RESULTS Of 70,060 individuals initiating both ChEIs and NSAIDs, we identified 1500 persons with peptic ulcer (median age at peptic ulcer 80 years), of whom 58% were females. Compared with the non-treatment periods, the risk of peptic ulcer substantially increased for the combination of ChEIs and NSAIDs (IRR: 9.0, [6.8-11.8]), more than for NSAIDs alone (5.2, [4.4-6.0]). No increased risks were found for the use of ChEIs alone (1.0, [0.9-1.2]). DISCUSSION We found that the risk of peptic ulcer associated with the concomitant use of NSAIDs and ChEIs was over and beyond the risk associated with NSAIDs alone. Our results underscore the importance of carefully considering the risk of peptic ulcers when co-prescribing NSAIDs and ChEIs to adults aged 65 years and older.
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Affiliation(s)
- Máté Szilcz
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Jonas W Wastesson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet & Stockholm University, Stockholm, Sweden
| | - Amaia Calderón-Larrañaga
- Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet & Stockholm University, Stockholm, Sweden
- Stockholm Gerontology Research Center, Stockholm, Sweden
| | - Daniel Prieto-Alhambra
- Centre for Statistics in Medicine, NDORMS, University of Oxford, Botnar Research Centre, Oxford, UK
- Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Pierre-Olivier Blotière
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Géric Maura
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Kristina Johnell
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
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Venturini CL, Damazo AS, Silva MJD, Muller JDAI, Oliveira DM, Figueiredo FDF, Serio BFD, Arunachalam K, Martins DTDO. Antiulcer activity and mechanism of action of the hydroethanolic extract of leaves of Terminalia argentea Mart. In different in vivo and in vitro experimental models. JOURNAL OF ETHNOPHARMACOLOGY 2024; 318:116972. [PMID: 37517568 DOI: 10.1016/j.jep.2023.116972] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/17/2023] [Revised: 07/24/2023] [Accepted: 07/27/2023] [Indexed: 08/01/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Terminalia argentea Mart. (Combretaceae) is a deciduous tree commonly found in Brazil, Bolivia, and Paraguay. It occurs in all regions of Brazil and is widespread in the Amazon, Cerrado, Pantanal, Atlantic Rain Forest, and Caatinga Biomes. In the traditional medicine of Brazil, people widely use tea or decoction of its leaf materials for treating gastritis, ulcers, wound healing, and inflammation. AIM OF THE STUDY The current study aims to evaluate the gastroprotective and ulcer-healing activities of the hydroethanolic extract of T. argentea leaves (HETa) and investigate the underlying mechanisms of action through in vivo and in vitro experiments. METHODS We extracted the leaves of T. argentea with a 70% hydroethanolic solution (HETa) and performed phytochemical analysis using high-performance liquid chromatography (HPLC) and electrospray ionization mass spectrometry (ESI-MSn). We researched the antiulcer activity using in vivo and in vitro experiments, administering three doses (2, 10, and 50 mg/kg) and different concentrations of 1, 5, and 20 μg/mL, respectively. We verified the acute antiulcer activity using chemical models (acidified ethanol (EtOH/HCl) and indomethacin (IND)) and physiological models (water-immersion stress (WRS)). To induce chronic ulcers, used acetic acid and treated the animals for seven days. To investigate the mechanism of action, conducted assays of antioxidant activity, measured the dosage of inflammatory cytokines, quantified mucus, treated with inhibitors (IND, L-NAME, glibenclamide, and yohimbine), performed histopathological analysis, and measured gastric acid secretion. Furthermore, we performed in vitro experiments on murine macrophage cell lines (RAW 264-7 cells) to quantify nitrite/nitrate and cytokine production and on V79-4 cells to verify cell proliferation/migration. RESULTS We conducted HPLC and ESI-MSn analyses to obtain a fingerprint of the chemical composition of the HETa, revealing the presence of phenolics (caffeoyl ellagic acid), flavonoids (rutin, quercetin xyloside, quercetin rhamnoside, quercetin glucoside, quercetin galloyl xyloside, quercetin), and tannins (terminalin), respectively. The three doses of HETa reduced acute and chronic ulcers in different models. The mechanism of action involves increasing mucus production and angiogenesis, and it partially involves prostaglandins, nitric oxide, K+ATP channels, and α2-adrenergic receptors. HETa also exhibited antioxidant potential, reducing myeloperoxidase (MPO) activity, and increasing glutathione (GSH) levels. Moreover, it demonstrated anti-inflammatory action by reducing nitrite/nitrate levels and pro-inflammatory cytokine concentrations in vivo, and it increased in vitro proliferation/migration of fibroblasts. CONCLUSIONS The study shows that HETa presents a potent preventive and curative antiulcer effect in different ulcer models, supporting the popular use of homemade preparations of T. argentea leaves. The preventive and gastric healing ulcer activity of HETa involves multiple targets, including increasing the gastric mucus barrier, antioxidant defenses, and anti-inflammatory effects on gastric mucosa repair. Phytochemical analysis identified the presence of phenolic compounds, flavonoids, and tannins in HETa, and the antiulcer activity may be attributable to the combined effect of these constituents.
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Affiliation(s)
- Claudio Luis Venturini
- Pharmacology Laboratory, Post-Graduate Program in Health Sciences, Federal University of Mato Grosso (UFMT), Cuiabá, MT, Brazil; Pharmacology Laboratory, Department of Basic Sciences in Health, Federal University of Mato Grosso (UFMT), Cuiabá, MT, Brazil.
| | - Amilcar Sabino Damazo
- Histology Laboratory, Department of Basic Sciences in Health, Federal University of Mato Grosso (UFMT), Cuiabá, MT, Brazil.
| | - Marcelo José Dias Silva
- Laboratory of Medicinal Plants and Herbal Medicines, Federal University of Alfenas (UNIFAL-MG), Rua Gabriel Monteiro da Silva, 700, Centro, Alfenas, Minas Gerais, Brazil.
| | - Jessica de Araujo Isaias Muller
- Pharmacology Laboratory, Post-Graduate Program in Health Sciences, Federal University of Mato Grosso (UFMT), Cuiabá, MT, Brazil.
| | - Darley Maria Oliveira
- Institute of Health Sciences, Federal University of Mato Grosso (UFMT), Sinop Campus, Mato Grosso, Brazil.
| | - Fabiana de Freitas Figueiredo
- Pharmacology Laboratory, Post-Graduate Program in Health Sciences, Federal University of Mato Grosso (UFMT), Cuiabá, MT, Brazil.
| | - Bruna Fioravante Di Serio
- Pharmacology Laboratory, Post-Graduate Program in Health Sciences, Federal University of Mato Grosso (UFMT), Cuiabá, MT, Brazil.
| | - Karuppusamy Arunachalam
- Center for Studies in Stem Cells, Cell Therapy and Toxicological Genetics (CeTroGen), Faculty of Medicine, Federal University of Mato Grosso Do Sul (UFMS), Campo Grande, 79070-900, MS, Brazil; Post-Graduate Program in Health and Development of the Midwest Region, Federal University of Mato Grosso Do Sul (UFMS), Campo Grande, 79070-900, MS, Brazil.
| | - Domingos Tabajara de Oliveira Martins
- Pharmacology Laboratory, Post-Graduate Program in Health Sciences, Federal University of Mato Grosso (UFMT), Cuiabá, MT, Brazil; Pharmacology Laboratory, Department of Basic Sciences in Health, Federal University of Mato Grosso (UFMT), Cuiabá, MT, Brazil.
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Shaukat TM, Omer MO, Javeed A, Rehman HU, Shaukat TM. Isolation of alkaloidal and glycosidal fractions from leaves of Trigonella foenum-graecum L. cv. Desi indigenous to Pakistan for antiprostaglandin evaluation as substitute of nonsteroidal anti-inflammatory drugs. JOURNAL OF ETHNOPHARMACOLOGY 2023; 317:116730. [PMID: 37336337 DOI: 10.1016/j.jep.2023.116730] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Revised: 05/24/2023] [Accepted: 06/02/2023] [Indexed: 06/21/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Trigonella foenum graecum (fenugreek) has been in use for a long time as a traditional medicine and natural food additive. The reported gastro-protective property makes it unique among other herbs. Seeds and leaves have been shown to exert significant antiatherogenic, antidiabetic, antianorexic, antioxidant, anticarcinogenic, antihyperlipidemic, galactogogue and anti-inflammatory effects in several animal and human models. But its use as a substitute for ulcerative nonsteroidal anti-inflammatory drugs needs to be confirmed. AIM OF THE STUDY Nonsteroidal anti-inflammatory drugs (NSAIDs) are in common use in treating inflammation associated with a variety of ailments, fever and pain such as menstrual cramps, back pain, arthritic pain and headaches. Their toxicity profile includes the risk of severe gastro-intestinal adverse events like increased bleeding tendency, ulceration, perforation, etc. Conventional NSAIDs have also been reported to reduce the glomerular filtration rate (GFR) by affecting afferent arterioles in nephrons. Exacerbated potassium levels were noted in patients using NSAIDs concomitantly with antihypertensive drugs belonging to the angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) classes. In this context, the need of the hour is to discover and isolate new compounds from the reported medicinal plants for evaluation of antiprostaglandin potential and safety profile in terms of the hepato-renal system. These compounds may be used as substitutes for NSAIDs in the future management of inflammation and pain with therapeutic equivalency and organ safety. In this scenario, the present study aimed to assess the antiprostaglandin potential of alkaloidal and glycosidal fractions from the leaves of Trigonella foenum-graecum L. cv. Desi variety, indigenous to Pakistan, in albino mice along with safety profile. The herb has been used as folk medicine since ancient times for treating inflammation and pain. MATERIAL AND METHODS Alkaloidal and glycosidal fractions were separated from a methanol extract of leaves of the fenugreek Desi variety. After separation of fractions, their subsiding effects on carrageenan-induced inflammation, air pouch exudate prostaglandin-E2 levels, Brewer's yeast induced pyrexia and acetic acid induced abdominal constrictions were assessed in adult male albino mice. The safety profile of fractions was assessed by measuring their effects on mice sera hepato-renal biomarkers. RESULT Alkaloidal fraction of T. foenum Desi variety was found to be significantly effective in reducing inflammation, air pouch exudate PGE2 levels, fever (≤37 °C) and pain by inhibiting writhes (up to 96.58%) Gradual inhibition of paw edema was observed 1-6 h post-dose, with maximum reduction percentages of 62.82% and 62.57% for 100 mg and 200 mg, respectively. Both fractions did not disturb the normal physiology of the hepato-renal system by showing normal biomarker values. CONCLUSION In summary, the results demonstrate the potent antiprostaglandin potential of the alkaloidal fraction of gastroprotective fenugreek "Desi" leaves with hepato-renal system safety and hence justify its use as a substitute for ulcerative nonsteroidal anti-inflammatory drugs.
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Affiliation(s)
- Tahir Mahmood Shaukat
- Department of Pharmacology and Toxicology, University of Veterinary and Animal Sciences, Lahore, 54000, Pakistan.
| | - Muhammad Ovais Omer
- Department of Pharmacology and Toxicology, University of Veterinary and Animal Sciences, Lahore, 54000, Pakistan.
| | - Aqeel Javeed
- Department of Pharmacology and Toxicology, University of Veterinary and Animal Sciences, Lahore, 54000, Pakistan
| | - Habib Ur Rehman
- Department of Physiology, University of Veterinary and Animal Sciences, Lahore, 54000, Pakistan
| | - Tariq Mahmood Shaukat
- Institute of Microbiology, University of Veterinary and Animal Sciences, Lahore, 54000, Pakistan
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Yang F, Wu Y, Hockey R, Doust J, Mishra GD, Montgomery GW, Mortlock S. Evidence of shared genetic factors in the etiology of gastrointestinal disorders and endometriosis and clinical implications for disease management. Cell Rep Med 2023; 4:101250. [PMID: 37909040 PMCID: PMC10694629 DOI: 10.1016/j.xcrm.2023.101250] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Revised: 03/26/2023] [Accepted: 09/27/2023] [Indexed: 11/02/2023]
Abstract
In clinical practice, the co-existence of endometriosis and gastrointestinal symptoms is often observed. Using large-scale datasets, we report a genetic correlation between endometriosis and irritable bowel syndrome (IBS), peptic ulcer disease (PUD), gastro-esophageal reflux disease (GORD), and a combined GORD/PUD medicated (GPM) phenotype. Mendelian randomization analyses support a causal relationship between genetic predisposition to endometriosis and IBS and GPM. Identification of shared risk loci highlights biological pathways that may contribute to the pathogenesis of both diseases, including estrogen regulation and inflammation, and potential therapeutic drug targets (CCKBR; PDE4B). Higher use of IBS, GORD, and PUD medications in women with endometriosis and higher use of hormone therapies in women with IBS, GORD, and PUD, support the co-occurrence of these conditions and highlight the potential for drug repositioning and drug contraindications. Our results provide evidence of shared disease etiology and have important clinical implications for diagnostic and treatment decisions for both diseases.
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Affiliation(s)
- Fei Yang
- The Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia
| | - Yeda Wu
- The Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia
| | - Richard Hockey
- The University of Queensland, NHMRC Centre for Research Excellence on Women and Non-communicable Diseases (CREWaND), School of Public Health, Herston Road, Herston, QLD, Australia
| | - Jenny Doust
- The University of Queensland, NHMRC Centre for Research Excellence on Women and Non-communicable Diseases (CREWaND), School of Public Health, Herston Road, Herston, QLD, Australia
| | - Gita D Mishra
- The University of Queensland, NHMRC Centre for Research Excellence on Women and Non-communicable Diseases (CREWaND), School of Public Health, Herston Road, Herston, QLD, Australia
| | - Grant W Montgomery
- The Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia
| | - Sally Mortlock
- The Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia.
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Toumi A, Abdella FI, Boudriga S, Alanazi TYA, Alshamari AK, Alrashdi AA, Dbeibia A, Hamden K, Daoud I, Knorr M, Kirchhoff JL, Strohmann C. Synthesis of Tetracyclic Spirooxindolepyrrolidine-Engrafted Hydantoin Scaffolds: Crystallographic Analysis, Molecular Docking Studies and Evaluation of Their Antimicrobial, Anti-Inflammatory and Analgesic Activities. Molecules 2023; 28:7443. [PMID: 37959862 PMCID: PMC10650415 DOI: 10.3390/molecules28217443] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Revised: 10/19/2023] [Accepted: 11/01/2023] [Indexed: 11/15/2023] Open
Abstract
In a sustained search for novel potential drug candidates with multispectrum therapeutic application, a series of novel spirooxindoles was designed and synthesized via regioselective three-component reaction between isatin derivatives, 2-phenylglycine and diverse arylidene-imidazolidine-2,4-diones (Hydantoins). The suggested stereochemistry was ascertained by an X-ray diffraction study and NMR spectroscopy. The resulting tetracyclic heterocycles were screened for their in vitro and in vivo anti-inflammatory and analgesic activity and for their in vitro antimicrobial potency. In vitro antibacterial screening revealed that several derivatives exhibited remarkable growth inhibition against different targeted microorganisms. All tested compounds showed excellent activity against the Micrococccus luteus strain (93.75 µg/mL ≤ MIC ≤ 375 µg/mL) as compared to the reference drug tetracycline (MIC = 500 µg/mL). Compound 4e bearing a p-chlorophenyl group on the pyrrolidine ring exhibited the greatest antifungal potential toward Candida albicans and Candida krusei (MIC values of 23.43 µg/mL and 46.87 µg/mL, respectively) as compared to Amphotericin B (MIC = 31.25 and 62.50 µg/mL, respectively). The target compounds were also tested in vitro against the lipoxygenase-5 (LOX-5) enzyme. Compounds 4i and 4l showed significant inhibitory activity with IC50 = 1.09 mg/mL and IC50 = 1.01 mg/mL, respectively, more potent than the parent drug, diclofenac sodium (IC50 = 1.19 mg/mL). In addition, in vivo evaluation of anti-inflammatory and analgesic activity of these spirooxindoles were assessed through carrageenan-induced paw edema and acetic acid-induced writhing assays, respectively, revealing promising results. In silico molecular docking and predictive ADMET studies for the more active spirocompounds were also carried out.
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Affiliation(s)
- Amani Toumi
- Laboratory of Heterocyclic Chemistry Natural Product and Reactivity (LR11ES39), Department of Chemistry, Faculty of Science of Monastir, University of Monastir, Monastir 5019, Tunisia;
| | - Faiza I.A. Abdella
- Department of Chemistry, College of Science, Ha’il University, Ha’il 81451, Saudi Arabia (T.Y.A.A.)
| | - Sarra Boudriga
- Laboratory of Heterocyclic Chemistry Natural Product and Reactivity (LR11ES39), Department of Chemistry, Faculty of Science of Monastir, University of Monastir, Monastir 5019, Tunisia;
| | - Tahani Y. A. Alanazi
- Department of Chemistry, College of Science, Ha’il University, Ha’il 81451, Saudi Arabia (T.Y.A.A.)
| | - Asma K. Alshamari
- Department of Chemistry, College of Science, Ha’il University, Ha’il 81451, Saudi Arabia (T.Y.A.A.)
| | | | - Amal Dbeibia
- Laboratory of Analysis, Treatment and Valorization of Environmental Pollutants and Products, Faculty of Pharmacy, University of Monastir, Monastir 5019, Tunisia;
| | - Khaled Hamden
- Laboratory of Bioresources: Integrative Biology and Valorization, Higher Institute of Biotechnology of Monastir, University of Monastir, Monastir 5000, Tunisia;
| | - Ismail Daoud
- Department of Matter Sciences, University of Mohamed Khider, BP 145 RP, Biskra 07000, Algeria;
- Laboratory of Natural and Bio-Actives Substances, Faculty of Science, Tlemcen University, P.O. Box 119, Tlemcen 13000, Algeria
| | - Michael Knorr
- Institut UTINAM-UMR CNRS 6213, Université de Franche-Comté, 16 Route de Gray, 25030 Besançon, France
| | - Jan-Lukas Kirchhoff
- Faculty of Chemistry, Inorganic Chemistry, Technical University Dortmund, Otto-Hahn-Strasse 6, 44227 Dortmund, Germany; (J.-L.K.); (C.S.)
| | - Carsten Strohmann
- Faculty of Chemistry, Inorganic Chemistry, Technical University Dortmund, Otto-Hahn-Strasse 6, 44227 Dortmund, Germany; (J.-L.K.); (C.S.)
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Chandra P, Kaleem M, Sachan N, Pathak R, Alanazi AS, Alsaif NA, Alsanea S, Alsuwayt B, Alanazi MM, Kabra A. Gastroprotective evaluation of Medicago sativa L. (Fabaceae) on diabetic rats. Saudi Pharm J 2023; 31:101815. [PMID: 37860685 PMCID: PMC10582054 DOI: 10.1016/j.jsps.2023.101815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2023] [Accepted: 10/01/2023] [Indexed: 10/21/2023] Open
Abstract
Traditional uses for the plant Medicago sativa (M. sativa) (Alfalfa) (Family: Fabaceae) include liver protection, antioxidant activity, and the treatment of bleeding and digestive issues. This study aims to assess the effect of ethanol extract of M. sativa (EEMS) on experimental-induced ulcers in diabetic rats. By pylorus ligation and ethanol administration, gastric ulcers were induced in diabetic rats. Five groups each consisting of six rats in each model were used. All other groups except Group I were made diabetic by giving rats alloxan (140 mg/kg i.p.). Vehicles were given to Group I (normal control) and Group II (diabetes control) rats. Group III (positive control) received ranitidine 50 mg/kg, and Group IV and V received EEMS at doses of 100 and 400 mg/kg, respectively. In the pylorus ligation and ethanol-induced stomach ulcer model of rats, the findings demonstrated that EEMS (100 mg/kg) showed a decreased ulcer index of 2.01 ± 0.41 and was found statistically significant against the diabetes control group (p < 0.001) as well as, an ulcer index of 0.68 ± 0.22 by EEMS (400 mg/kg) with a significant reduction in the ulcer index (p < 0.001). EEMS (100 and 400 mg/kg) reduce free acidity by 13.16 ± 0.65 mEq/L and 9.83 ± 0.30 mEq/L, respectively. EEMS also showed a protective impact on the liver and kidneys of diabetic rats. Antihyperglycemic action was also discovered in diabetic animals. The findings of the current investigation demonstrated that ethanolic extract of M. sativa possesses anti-ulcer activity in diabetic rats. Ethanolic extract of M. sativa may be a treatment option for stomach ulcers that also have diabetes.
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Affiliation(s)
- Phool Chandra
- Teerthanker Mahaveer College of Pharmacy, Teerthanker Mahaveer University, Moradabad, U.P. 244001, India
| | - Mohammad Kaleem
- School of Pharmaceutical Sciences, IFTM University, Lodhipur Rajput, Delhi Road (NH-24), Moradabad 244 102, U.P., India
| | - Neetu Sachan
- Maharana Pratap College of Pharmacy, Mandhana, Kanpur 209217, U.P., India
| | - Rashmi Pathak
- Department of Pharmacy, Invertis University, Bareilly 243123, U.P., India
| | - Ashwag S. Alanazi
- Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia
| | - Nawaf A. Alsaif
- Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia
| | - Sary Alsanea
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
| | - Bader Alsuwayt
- Department of Pharmacy Practice, College of Pharmacy, University of Hafr Al-Batin, Hafr Al-Batin 31991, Saudi Arabia
| | - Mohammed M. Alanazi
- Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia
| | - Atul Kabra
- University Institute of Pharma Sciences, Chandigarh University, Mohali 140301, Punjab, India
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Yahya H. Change in Prevalence and Pattern of Peptic Ulcer Disease in the Northern Savannah of Nigeria: An Endoscopic Study. Ann Afr Med 2023; 22:420-425. [PMID: 38358140 PMCID: PMC10775940 DOI: 10.4103/aam.aam_144_22] [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: 10/14/2022] [Accepted: 01/04/2023] [Indexed: 02/16/2024] Open
Abstract
Background Peptic ulcer disease (PUD) is common worldwide. Its incidence and prevalence have been declining in recent years in developed countries, and a similar trend has been observed in many parts of Africa including Nigeria. Aim This study aimed to provide an endoscopic update on PUD in the Northern Savannah of Nigeria and compare with past reports from the region and recent reports from Nigeria, Africa, and the rest of the world. Methods Upper gastrointestinal endoscopy records of consecutive patients diagnosed with PUD between January 2014 and September 2022 at an endoscopy unit of a tertiary institution in North-West Nigeria were retrieved and demographic data, types of peptic ulcer, and their characteristics were extracted and analyzed. Results Over a 9-year period, 171/1958 (8.7%) patients were diagnosed with PUD: mean age 48.8 years (range 14-85), 68.4% male, and 70% >40 years. 59.6% were gastric ulcers (GU), 31.6% duodenal ulcers (DU), and 8.8% were both. The mean age of patients with GU was slightly higher than those with DU (49.9 years vs. 46.6 years, P = 0.29); patients aged <40 years were significantly more likely to be diagnosed with DU than GU (54.7% vs. 33.9%, P = 0.016) while those >40 years significantly more GU than DU (74.6% vs. 54.7%, P = 0.016). There were no significant gender differences between GU and DU. Conclusion The prevalence and pattern of PUD in Northern Savannah of Nigeria have changed - patients were predominantly male and older, and GU predominated.
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Affiliation(s)
- Husain Yahya
- Department of Internal Medicine, Barau Dikko Teaching Hospital, Kaduna State University, Kaduna, Nigeria
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Prasher P, Sharma M. Layered double hydroxide nanocarriers: potential delivery systems for mefenamic acid. Nanomedicine (Lond) 2023; 18:1697-1701. [PMID: 37877695 DOI: 10.2217/nnm-2023-0217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2023] Open
Abstract
Tweetable abstract Layered double hydroxide nanocarriers are capable of intercalating hydrophobic NSAIDs, such as mefenamic acid, which improves their pharmacokinetics and bioavailability.
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Affiliation(s)
- Parteek Prasher
- Department of Chemistry, University of Petroleum & Energy Studies, Energy Acres, Dehradun, 248007, India
| | - Mousmee Sharma
- Department of Chemistry, Uttaranchal University, Dehradun, 248007, India
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Salame M, Teixeira AF, Lind R, Ungson G, Ghanem M, Abi Mosleh K, Jawad MA, Abu Dayyeh BK, Kendrick ML, Ghanem OM. Marginal Ulcer and Dumping Syndrome in Patients after Duodenal Switch: A Multi-Centered Study. J Clin Med 2023; 12:5600. [PMID: 37685666 PMCID: PMC10488365 DOI: 10.3390/jcm12175600] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Revised: 08/15/2023] [Accepted: 08/24/2023] [Indexed: 09/10/2023] Open
Abstract
BACKGROUND The current design of biliopancreatic diversion with duodenal switch (BPD/DS) and single anastomosis duodenal-ileal bypass with sleeve (SADI-S) emphasizes the importance of the pylorus' preservation to reduce the incidence of marginal ulcer (MU) and dumping. However, no institutional studies have yet reported data on their prevalence. We aimed to assess the incidence of MU and dumping after duodenal switch (DS) and identify the associative factors. METHODS A multi-center review of patients who underwent BPD/DS or SADI-S between 2008 and 2022. Baseline demographics, symptoms, and management of both complications were collected. Fisher's exact test was used for categorical variables and the independent t-test for continuous variables. RESULTS A total of 919 patients were included (74.6% female; age 42.5 years; BMI 54.6 kg/m2) with mean follow-up of 31.5 months. Eight patients (0.9%) developed MU and seven (0.8%) had dumping. Patients who developed MU were more likely to be using non-steroidal anti-inflammatory drugs (NSAID) (p = 0.006) and have a longer operation time (p = 0.047). Primary versus revisional surgery, and BDP/DS versus SADI-S were not associated with MU or dumping. CONCLUSIONS The incidences of MU and dumping after DS were low. NSAID use and a longer operation time were associated with an increased risk of MU, whereas dumping was attributed to poor dietary habits.
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Affiliation(s)
- Marita Salame
- Department of Surgery, Mayo Clinic, Rochester, MN 55905, USA
| | | | - Romulo Lind
- Department of Surgery, Orlando Health, Orlando, FL 32806, USA
| | - Gilberto Ungson
- Department of Surgery, Cima Hospital, Hermosillo 83280, Mexico
| | - Muhammad Ghanem
- Department of Surgery, Orlando Health, Orlando, FL 32806, USA
| | | | | | - Barham K. Abu Dayyeh
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA
| | | | - Omar M. Ghanem
- Department of Surgery, Mayo Clinic, Rochester, MN 55905, USA
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Subhawa S, Arpornchayanon W, Jaijoy K, Chansakaow S, Soonthornchareonnon N, Sireeratawong S. Anti-Inflammatory, Antinociceptive, Antipyretic, and Gastroprotective Effects of Eurycoma longifolia Jack Ethanolic Extract. Life (Basel) 2023; 13:1465. [PMID: 37511840 PMCID: PMC10381342 DOI: 10.3390/life13071465] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Revised: 06/25/2023] [Accepted: 06/26/2023] [Indexed: 07/30/2023] Open
Abstract
Tongkat ali (Eurycoma longifolia Jack) (ELJ) is a plant in the Simaroubaceae family. Its roots are used in traditional Thai medicine to treat inflammation, pain, and fever; however, the antiulcer abilities of its ethanolic extract have not been studied. This study examined the anti-inflammatory, antinociceptive, antipyretic, and gastroprotective effects of ethanolic ELJ extract in animal models and found that ELJ effectively reduced EPP-induced ear edema in a dose-dependent manner and that a high dose of ELJ inhibited carrageenan-induced hind paw edema formation. In cotton-pellet-induced granuloma formation, a high dose of ELJ suppressed the increases in wet granuloma weight but not dry or transudative weight. In the formalin-induced nociception study, ELJ had a significant dose-dependent inhibitory impact. Additionally, the study found that yeast-induced hyperthermia could be significantly reduced by antipyretic action at the highest dose of ELJ. In all the gastric ulcer models induced by chemical substances or physical activity, ELJ extracts at 150, 300, and 600 mg/kg also effectively prevented gastric ulcer formation. In the pyloric ligation model, however, the effects of ELJ extract on gastric volume, gastric pH, and total acidity were statistically insignificant. These findings support the current widespread use of Eurycoma longifolia Jack in traditional medicine, suggest the plant's medicinal potential for development of phytomedicines with anti-inflammatory, antinociceptive, and antipyretic properties, and support its use in the treatment of gastric ulcers due to its gastroprotective properties.
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Affiliation(s)
- Subhawat Subhawa
- Clinical Research Center for Food and Herbal Product Trials and Development (CR-FAH), Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
- Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
| | | | - Kanjana Jaijoy
- McCormick Faculty of Nursing, Payap University, Chiang Mai 50000, Thailand
| | - Sunee Chansakaow
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand
| | | | - Seewaboon Sireeratawong
- Clinical Research Center for Food and Herbal Product Trials and Development (CR-FAH), Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
- Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
- Department of Preclinical Science, Division of Pharmacology, Faculty of Medicine, Rungsit Campus, Thammasat University, Pathum Thani 12120, Thailand
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McKay S, Cohran V, Bass LM. Anastomotic Ulcers: Current Understanding of the Pathogenesis and Management. Curr Gastroenterol Rep 2023:10.1007/s11894-023-00873-w. [PMID: 37303027 DOI: 10.1007/s11894-023-00873-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/26/2023] [Indexed: 06/13/2023]
Abstract
PURPOSE OF REVIEW Anastomotic ulceration following intestinal resection is an under- recognized problem in pediatrics. We discuss the relevant literature regarding this condition. RECENT FINDINGS Anastomotic Ulceration following intestinal resection is a potentially life threatening cause of refractory anemia. Evaluation should include correction of micronutrient deficiencies and endoscopic evaluation by upper and lower endoscopy and small intestinal endoscopy if necessary. Initial treatment by medical therapy may consist of anti-inflammatory agents as well as antibiotics to treat small intestinal bacterial overgrowth. Surgical resection should be considered if refractory to treatment. Anastomotic ulcers in pediatric patients with small bowel resection should be considered as a cause of refractory iron deficiency anemia. Endoscopic evaluation should be undertaken to look for evidence of anastomotic ulcers. Surgical resection should be considered if medical therapy fails.
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Affiliation(s)
- Shaunte McKay
- Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, 225 E. Chicago Ave Box #65, Chicago, IL, 60611, USA
| | - Valeria Cohran
- Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, 225 E. Chicago Ave Box #65, Chicago, IL, 60611, USA
| | - Lee M Bass
- Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, 225 E. Chicago Ave Box #65, Chicago, IL, 60611, USA.
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Anish RJ, Mohanan B, Aswathy TR, Nair A, Radhakrishnan KV, Rauf AA. An integrated approach to the structural characterization, long-term toxicological and anti-inflammatory evaluation of Pterospermum rubiginosum bark extract. JOURNAL OF ETHNOPHARMACOLOGY 2023; 308:116262. [PMID: 36796743 DOI: 10.1016/j.jep.2023.116262] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Revised: 02/06/2023] [Accepted: 02/08/2023] [Indexed: 06/18/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE OF STUDY Pterospermum rubiginosum is an evergreen plant in Western Ghats, India, used by traditional tribal healers due to its excellent biological potential for treating inflammation and pain relief procedures. The bark extract is also consumed to relieve the inflammatory changes at the bone fractured site. The traditional medicinal plant in India have to be characterized for its diverse phytochemical moieties, its interactive multiple target sites, and to reveal the hidden molecular mechanism behind the biological potency. AIM OF THE STUDY The study focussed on plant material characterization, computational analysis (prediction study), toxicological screening (In vivo), and anti-inflammatory evaluation of P. rubiginosum methanolic bark extracts (PRME) in LPS-induced RAW 264.7 cells. MATERIALS AND METHODS The pure compound isolation of PRME and their biological interactions were used to predict the bioactive components, molecular targets, and molecular pathways of PRME in inhibiting inflammatory mediators. The anti-inflammatory effects of PRME extract were evaluated in the lipopolysaccharide (LPS)-induced RAW264.7 macrophage cell model. The toxicity evaluation of PRME was performed in healthy 30 Sprague-Dawley experimental rats, were randomly divided into five groups for toxicological evaluation for 90 days. The tissue levels of oxidative stress and organ toxicity markers were measured using the ELISA method. Nuclear magnetic resonance spectroscopy (NMR) was performed to characterize the bioactive molecules. RESULTS Structural characterization revealed the presence of vanillic acid, 4-O-methyl gallic acid, E-resveratrol, gallocatechin, 4'-O-methyl gallocatechin, and catechin. Molecular docking of NF-kB exhibited significant interactions with vanillic acid and 4-O-methyl gallic acid with binding energy -351.159 Kcal/Mol and -326.5505 Kcal/Mol, respectively. The PRME-treated animals showed an increase in total GPx and antioxidant levels (SOD and catalase). Histopathological examination revealed no variation in the liver, renal and splenic tissue's cellular pattern. PRME inhibited the pro-inflammatory parameters (IL-1β, IL-6, and TNF-α) in LPS-induced RAW 264.7 cells. The protein level of TNF-α and NF-kB protein expression study brought out a notable reduction and exhibited a good correlation with the gene expression study. CONCLUSION The current study establishes the therapeutic potential of PRME as an effective inhibitory agent against LPS-activated RAW 264.7 cells induced inflammatory mediators. Long-term toxicity evaluation on SD rats confirmed the non-toxic nature of PRME up to 250mg/body weight for 3 months.
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Affiliation(s)
| | - Biji Mohanan
- Chemical Sciences and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology (CSIR-NIIST), Thiruvananthapuram, 695019, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India.
| | | | - Aswathy Nair
- Kerala State Palmyrah Products Development and Workers' Welfare Corporation Limited, Trivandrum, 695122, India.
| | - K V Radhakrishnan
- Chemical Sciences and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology (CSIR-NIIST), Thiruvananthapuram, 695019, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India.
| | - Arun A Rauf
- Department of Biochemistry, University of Kerala, Trivandrum, 695581, India.
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Palo SK, Nayak SR, Sahoo D, Nayak S, Mohapatra AK, Sahoo A, Dash P, Pati S. Prevalence and pattern of multimorbidity among chronic kidney disease patients: a community study in chronic kidney disease hotspot area of Eastern India. Front Med (Lausanne) 2023; 10:1131900. [PMID: 37250643 PMCID: PMC10213441 DOI: 10.3389/fmed.2023.1131900] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Accepted: 04/27/2023] [Indexed: 05/31/2023] Open
Abstract
Introduction Chronic kidney disease (CKD) is mostly asymptomatic until reaching an advanced stage. Although conditions such as hypertension and diabetes can cause it, CKD can itself lead to secondary hypertension and cardiovascular disease (CVD). Understanding the types and prevalence of associated chronic conditions among CKD patient could help improve screening for early detection and case management. Methods A cross sectional study of 252 CKD patients in Cuttack, Odisha (from the last 4 years CKD data base) was telephonically carried out using a validated Multimorbidity Assessment Questionnaire for Primary Care (MAQ-PC) tool with the help of an android Open Data Kit (ODK). Univariate descriptive analysis was done to determine the socio-demographic distribution of CKD patients. A Cramer's heat map was generated for showing Cramer's coefficient value of association of each diseases. Results The mean age of participants was 54.11 (±11.5) years and 83.7% were male. Among the participants, 92.9% had chronic conditions (24.2% with one, 26.2% with two and 42.5% with three or more chronic conditions). Most prevalent chronic conditions were hypertension (48.4%), peptic ulcer disease (29.4%), osteoarthritis (27.8%) and diabetes (13.1%). Hypertension and osteoarthritis were found to be most commonly associated (Cramer's V coefficient = 0.3). Conclusion Increased vulnerability to chronic conditions among CKD patients make them at higher risk for mortality and compromised quality of life. Regular screening of CKD patient for other chronic conditions (hypertension, diabetes, peptic ulcer disease, osteoarthritis and heart diseases) would help in detecting them early and undertake prompt management. The existing national program could be leveraged to achieve this.
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Affiliation(s)
| | | | - Debadutta Sahoo
- Model Rural Health Research Unit, ICMR-RMRCBB, Cuttack, India
| | - Swetalina Nayak
- Model Rural Health Research Unit, ICMR-RMRCBB, Cuttack, India
| | | | - Aviram Sahoo
- Model Rural Health Research Unit, ICMR-RMRCBB, Cuttack, India
| | - Pujarini Dash
- Model Rural Health Research Unit, ICMR-RMRCBB, Cuttack, India
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Upadhyay C, D'Souza A, Patel P, Verma V, Upadhayay KK, Bharkatiya M. Inclusion Complex of Ibuprofen-β-Cyclodextrin Incorporated in Gel for Mucosal Delivery: Optimization Using an Experimental Design. AAPS PharmSciTech 2023; 24:100. [PMID: 37029312 DOI: 10.1208/s12249-023-02534-7] [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: 09/20/2022] [Accepted: 02/12/2023] [Indexed: 04/09/2023] Open
Abstract
β-Cyclodextrin/ibuprofen inclusion complex was synthesized by freeze-drying method and characterized for phase solubility profiles, infrared spectra, thermal analysis, and X-ray powder diffractograms. The inclusion complex with HP-β-CD, as confirmed by molecular dynamics simulations, enhanced the aqueous solubility of ibuprofen by almost 30-fold compared to ibuprofen alone. Different grades of Carbopol (Carbopol 934P/Carbopol 974P/Carbopol 980 NF/Carbopol Ultrez 10 NF) and cellulose derivatives (HPMC K100M/HPMC K15M/HPMC K4M/HPMC E15LV/HPC) were evaluated for mucoadhesive gels incorporating the inclusion complex. The central composite design generated by Design-Expert was employed to optimize the mucoadhesive gel using two independent variables (a varying combination of two gelling agents) on three dependent variables (drug content and in vitro drug release at 6 h and 12 h). Except for the methylcellulose-based gels, most of the gels (0.5%, 0.75%, and 1% alone or as a mixture thereof) exhibited an extended-release of ibuprofen, ranging from 40 to 74% over 24 h and followed the Korsmeyer-Peppas kinetics model. Using this test design, 0.95% Carbopol 934P and 0.55% HPC-L formulations were optimized to increase ibuprofen release, enhance mucoadhesion, and be non-irritating in ex vivo chorioallantoic membrane studies. The present study successfully developed a mucoadhesive gel containing the ibuprofen-β-cyclodextrin inclusion complex with sustained release.
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Affiliation(s)
| | - Anisha D'Souza
- School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania, USA
| | - Pratikkumar Patel
- Department of Chemical Sciences, Bernal Institute, University of Limerick, Limerick, Ireland
| | - Vivek Verma
- Department of Chemical Sciences, Bernal Institute, University of Limerick, Limerick, Ireland
| | | | - Meenakshi Bharkatiya
- B.N Institute of Pharmaceutical Sciences, B. N. University, Udaipur, Rajasthan, India.
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Park HJ, Ham HJ, Yang YJ, Seo MK, Kim HI, Lee JH. Liquid chromatography-quadrupole orbitrap and liquid chromatography-tandem mass spectrometry system for rapid identification and quantitation of thirty nonsteroidal anti-inflammatory drugs and acetaminophen in illegal products. RAPID COMMUNICATIONS IN MASS SPECTROMETRY : RCM 2023; 37:e9462. [PMID: 36567073 DOI: 10.1002/rcm.9462] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Revised: 12/21/2022] [Accepted: 12/22/2022] [Indexed: 06/17/2023]
Abstract
RATIONALE As the public interest in healthcare increases, illegal dietary supplements, foods, and drugs containing unauthorized pharmaceutical ingredients, including nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen, have been identified. Excessive and unintentional consumption is toxic to the gastrointestinal tract, kidneys, and liver; therefore, these pharmaceuticals must be monitored using analytical methods. METHODS A rapid and reliable analysis system involving liquid chromatography-quadrupole orbitrap mass spectrometry (LC-Q-Orbitrap/MS) and liquid chromatography-tandem mass spectrometry (LC/MS/MS) was established and validated to identify and quantify 30 NSAIDs and acetaminophen. In addition, we obtained the MS2 spectrum for each component with the proposed structure of the fragment ions. RESULTS The analytical method was applied to 505 samples of illicitly distributed dietary supplements, foods, and pharmaceuticals. Non-steroidal analgesics were detected in 126 samples. Carbamazepine (42.9%) and diclofenac (30.2%) were the most detected components in the samples; other pharmaceutical adulterants were also detected in some cases. Additionally, we present the identification of an unknown component, dexamethasone (799 μg/g), using LC-Q-Orbitrap/MS in a sample containing the unknown component with meloxicam (15.4 mg/g). CONCLUSIONS The developed analysis system, consisting of qualitative analysis using LC-Q-Orbitrap/MS and quantitative analysis using LC/MS/MS, can rapidly and accurately identify and quantify NSAIDs and acetaminophen while also identifying non-analytical components.
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Affiliation(s)
- Hyoung-Joon Park
- Center for Advanced Analysis, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Cheongju, Chungcheongbuk-do, Republic of Korea
| | - Hyeon Joo Ham
- Center for Advanced Analysis, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Cheongju, Chungcheongbuk-do, Republic of Korea
| | - Yoon Ji Yang
- Center for Advanced Analysis, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Cheongju, Chungcheongbuk-do, Republic of Korea
| | - Min Kyeong Seo
- Center for Advanced Analysis, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Cheongju, Chungcheongbuk-do, Republic of Korea
| | - Hyung Il Kim
- Center for Advanced Analysis, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Cheongju, Chungcheongbuk-do, Republic of Korea
| | - Ji Hyun Lee
- Center for Advanced Analysis, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Cheongju, Chungcheongbuk-do, Republic of Korea
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Molecular docking and anti-ulcerative potential of Cucumis (L. Inodorous) on ibuprofen induced gastric ulceration in male wistar animals. Biomed Pharmacother 2023; 161:114531. [PMID: 36934555 DOI: 10.1016/j.biopha.2023.114531] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Revised: 03/01/2023] [Accepted: 03/13/2023] [Indexed: 03/19/2023] Open
Abstract
BACKGROUND The use of NSAIDs have caused stomach injury by inhibiting endogenous mucosal prostaglandin production. Cucumis melo is reported to possess antiulcer potential. This study investigates the mechanism underlying the antiulcer potentials of Cucumis melo (CUM). METHODS Thirty-five male Wistar rat were randomly assigned to each of seven groups; A(control given water and rat pellets), B(gastric ulcer induced with ibuprofen 400 mg/kg), C (Misoprotol 200 μg/kg), D to G (pretreated with different variation of CUM extract; 25 %, 50 %, 75 % and 100 % at a dose of 1 ml/kg for 3 weeks prior to gastric ulcer induction). Ulcer score, ulcer index and percentage inhibition, total gastric acidity was measured. Antioxidant activities, Malondialdehyde, H+/K+ ATPase, PGE2, TNF-α was done by spectrophotometry. Molecular docking investigation of Cucumis melo compounds against Prostaglandin E2 was carried out. Level of significance was tested at P ≤ 0.05 using Tukey post hoc. RESULT Total gastric acidity, ulcer score, ulcer index, MDA, TNF-α significantly decreased after CUM treatment when compared to group B. The percentage inhibition, antioxidant activities, PGE2 concentration was significantly increased in all treatment groups compared to group B. Interactions of selected compounds of CUM with Prostaglandin E2 at various docking pockets showed folic acid has highest binding affinity followed by delta7-avenasterol and codisterol to PGE2 receptor. this study shows that one of the mechanisms by which CUM exhibits its antiulcer potential by enhancing Prostaglandin synthesis and antioxidant capacity. Therefore, Cucumis melo can therefore be explored as novel antiulcer agents.
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Tetz KB, Schoenbeck SL. Assessing pain-the invisible, long-haul polio symptom. Nursing 2023; 53:42-46. [PMID: 36820695 DOI: 10.1097/01.nurse.0000905720.83240.9b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/18/2023]
Abstract
Chronic pain is a common problem for polio survivors. Nurses are on the front line to assess the scope, severity, and impact of reported pain. This article describes how nurses can advocate for patients experiencing post-polio syndrome pain.
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Affiliation(s)
- Karen B Tetz
- At Walla Walla University School of Nursing in Portland, Ore., Karen Tetz is a professor of nursing and Susan Schoenbeck is a mentor
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Feasibility and Safety of Mesocolon Excision with Medical Imaging: A Systematic Review and Meta-Analysis. COMPUTATIONAL INTELLIGENCE AND NEUROSCIENCE 2023; 2023:6198625. [PMID: 36851940 PMCID: PMC9966824 DOI: 10.1155/2023/6198625] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Revised: 09/16/2022] [Accepted: 09/29/2022] [Indexed: 02/20/2023]
Abstract
The development of new technologies based on electronic intelligent images is a very active research and promotion of new technologies in recent years. This article mainly summarizes the basic concept, development, and technology of electronic intelligent imaging technology, as well as the research, promotion, and application of electronic intelligent imaging technology in clinical treatment. It especially emphasizes the practicality and application of electronic intelligent imaging technology in the current clinical operation process and conducts a meta-analysis of the current mesorectal excision, so as to provide more scientific and professional guidance for clinical surgery. The results of the meta-analysis showed that 3291 documents were initially obtained and duplicate documents were deleted by searching for keywords in mesocolon excision. We excluded 2399 subjects and articles whose interventions did not meet the inclusion criteria of this study after reading the title and abstract. Then, we obtained 892 papers that may meet the inclusion criteria through preliminary screening. We further optimized the search strategy based on selection criteria and data integrity filtering principles and finally determined 111 references. 100 articles that did not meet the requirements were excluded, and 11 articles were finally included for meta-analysis. Medical imaging can effectively improve the therapeutic effect of mesocolon excision and reduce the occurrence of complications. Therefore, it is very important to combine medical intelligent images for preoperative evaluation, and the development of the combination of surgical treatment and medical images should not be underestimated in the future.
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dos Santos JAA, de Araújo Moura BK, Pérez CD, Cavalcanti IDL, Lira Nogueira MCDB, Ximenes RM, de Aguiar Júnior FCA, Silva Santos NPD. Protective mucus effect of the crude fraction of the mucus produced by the zoanthide Palythoa caribaeorum. Tissue Cell 2022; 79:101957. [DOI: 10.1016/j.tice.2022.101957] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Revised: 10/10/2022] [Accepted: 10/11/2022] [Indexed: 11/17/2022]
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Toktay E, Selli J. Histopathological Overview of Experimental Ulcer Models. Eurasian J Med 2022; 54:120-126. [PMID: 36655455 PMCID: PMC11163344 DOI: 10.5152/eurasianjmed.2022.22312] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Accepted: 11/22/2022] [Indexed: 01/19/2023] Open
Abstract
Histopathology is the process of examining tissue that includes all the changes, when a diseased tissue shows compared to a healthy group with a result of a histological observation. Histopathology has become an essential process in medical experimental research and medical experimental models. Scientists have developed medical experimental animal models for these reasons and have pioneered new drug research for many years. One of these experimental researches is experimental ulcer models. This model, which was initially a single method, has led to the emergence of new models with the discovery of physiological processes on ulcers by scientists. Nowadays, researchers have performed many new peptic ulcer models on experimental animals over the years. The main point in the creation of the ulcer model is the increase in the stomach acid level and the removal or corruption of the gastric mucus. When the experimental models were examined histopathologically, it was seen that the most severe models were those induced by pyloric ligation, acetic acid application, and indomethacin. In these models, ulcer foci that progressed to the submucosa were common, while the superficial damage spreading to the entire surface was striking in the ethanol model. While epithelial losses are shown on the surface of the mucosa, foci of necrotic apoptotic cell clusters extending to the submucosa are shown according to the weight of the model. In addition, evidence of inflammation has been shared in almost all studies. All these results show that ulcer models can be created by many different mechanisms. However, similar findings were observed in almost all experiments. Whether the experimental model caused severe or mild ulceration changed the histological findings.
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Affiliation(s)
- Erdem Toktay
- Department of Histology and Embryology, Philosophy Doctor Degree, Faculty of Medicine, Kafkas University, Kars, Turkey
| | - Jale Selli
- Department of Histology and Embryology, Philosophy Doctor Degree, Faculty of Medicine, Alanya Alaaddin Keykubat University, Antalya, Turkey
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Russo J, Fiegel J, Brogden NK. Effect of Salt Form on Gelation and Drug Delivery Properties of Diclofenac-Loaded Poloxamer Gels for Delivery to Impaired Skin. Pharm Res 2022; 39:2515-2527. [PMID: 36002613 PMCID: PMC9578569 DOI: 10.1007/s11095-022-03356-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Accepted: 07/29/2022] [Indexed: 11/28/2022]
Abstract
PURPOSE Treating chronic wounds is a significant clinical challenge, and a topical product would be ideal for pain management. Poloxamer 407, a thermosensitive polymer, would allow an analgesic drug to be topically applied to a wound as a liquid that transitions to a gel at physiologic temperature. Using diclofenac as a model analgesic drug, our goal was to determine effects of salt form on poloxamer gelation and drug delivery from poloxamer gels applied to excised skin with impaired barrier function. METHODS Gelation properties of 17% and 20% poloxamer gels loaded with 0.4 to 1.7% diclofenac sodium, potassium, epolamine, or diethylamine were evaluated rheologically. Drug release and delivery were quantified using cellulose membranes, porcine skin, and tape-stripped porcine skin. RESULTS Poloxamer gelation temperature increased with higher diclofenac concentration, regardless of salt form; the magnitude of increase varied in the following order: sodium>potassium>diethylamine>epolamine. Gelation temperature differences resulting from the various counterions generally matched previously observed trends of ion-specific effects on macromolecule solubility (the Hofmeister series). Despite changes in gelation behavior, we observed minimal corresponding effects on drug release or delivery. There were no significant differences in diclofenac released or delivered through intact porcine skin over 48 h. However, in studies with impaired (tape-stripped) skin, diclofenac delivery was slowest overall with the epolamine salt. CONCLUSION Varying the salt form of a model analgesic drug can impact gelation and drug delivery characteristics of poloxamer systems. Further study of the mechanisms of these changes will be important for continued development of topical poloxamer products for clinical wound care.
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Affiliation(s)
- Jackson Russo
- Department of Pharmaceutical Sciences and Experimental Therapeutics, The University of Iowa, Iowa City, IA, 52242, USA
- The University of Iowa College of Pharmacy, 180 S. Grand Ave, Iowa City, IA, 52242, USA
| | - Jennifer Fiegel
- Department of Chemical and Biochemical Engineering, The University of Iowa, Iowa City, IA, 52242, USA
| | - Nicole K Brogden
- Department of Pharmaceutical Sciences and Experimental Therapeutics, The University of Iowa, Iowa City, IA, 52242, USA.
- The University of Iowa College of Pharmacy, 180 S. Grand Ave, Iowa City, IA, 52242, USA.
- Department of Dermatology, The University of Iowa, Iowa City, IA, 52242, USA.
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Protective effects of apelin on gastric mucosa. Tissue Cell 2022; 78:101885. [PMID: 35940035 DOI: 10.1016/j.tice.2022.101885] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 07/29/2022] [Accepted: 08/01/2022] [Indexed: 11/18/2022]
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Therapeutic Versus Preventative Use of Ginkgo biloba Extract (EGb 761) against Indomethacin-Induced Gastric Ulcer in Mice. Molecules 2022; 27:molecules27175598. [PMID: 36080365 PMCID: PMC9458100 DOI: 10.3390/molecules27175598] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 08/25/2022] [Accepted: 08/28/2022] [Indexed: 11/29/2022] Open
Abstract
The main bioactive constituents in the standardized Ginkgo biloba leaf extract (EGb 761) are the terpene lactones and flavonoid glycosides. EGb 761’s antioxidant and anti-inflammatory properties have previously been demonstrated. Indomethacin-induced gastric ulcers have a multifactorial etiology and represent a major restriction to its therapeutic utility. The underlying ulcerogenic process involves oxidative and inflammatory biomolecular insults. This study was performed to explore the curative and preventative benefits of EGb 761 in experimentally-induced ulcers. To develop gastric ulcers in mice, indomethacin (40 mg/kg) was administered orally. EGb 761 (200 mg/kg) was given by gavage for 7 days before (preventative) and after (therapeutic) indomethacin administration. The histological alterations and macroscopic mucosal lesions were assessed. In gastric tissue homogenates, malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO), and inflammatory cytokines were measured. The expressions of cyclooxygenase-2 (COX-2), cytokines, and proliferating cell nuclear antigen (PCNA) in the stomach mucosa were also investigated. The ulcer index, histological alterations, gastric oxidants, and inflammatory biomarkers were all significantly increased by indomethacin. In stomach specimens, it increased COX-2 and PCNA expression. EGb 761 treatments, both prophylactic and therapeutic, resulted in significant reductions in ulcer lesions, nitrosative and oxidative damage, and inflammatory markers, along with the lowering of COX-2 and PCNA expressions. Furthermore, in the fight against stomach ulcers, EGb 761 treatment was found to be more efficient than prevention.
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Anjani QK, Sabri AHB, Moreno-Castellanos N, Utomo E, Cárcamo-Martínez Á, Domínguez-Robles J, Wardoyo LAH, Donnelly RF. Soluplus®-based dissolving microarray patches loaded with colchicine: towards a minimally invasive treatment and management of gout. Biomater Sci 2022; 10:5838-5855. [PMID: 35972236 DOI: 10.1039/d2bm01068b] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Considered as one of the most common inflammatory arthritis, gout is characterised by a sudden onset of severe joint pain. As the first-line drug of choice used in treating acute gout, colchicine (CLC) is hindered by poor gastrointestinal permeability as well as unfavourable gastrointestinal side effects. Herein, we present, for the first time, the preparation of microarray array patches (MAPs) made of a polymeric solubiliser, Soluplus®, loaded with CLC for its systemic delivery. The fabricated MAPs displayed acceptable mechanical properties and were capable of being inserted into the skin to a depth of ≈500 μm in full thickness ex vivo neonatal porcine skin, as evidenced by optical coherence tomography. In vitro dermatokinetic studies utilising full thickness neonatal porcine skin demonstrated that the CLC-loaded MAPs delivered CLC across all skin strata, resulting in a delivery efficiency of 73% after 24 hours. Furthermore, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and cell proliferation assays along with LIVE/DEAD™ staining on the 3T3-L1 cell line showed that the MAP formulation displayed minimal toxicity, with acceptable biocompatibility. Lastly, the anti-inflammatory properties of the formulation were evaluated using a THP-1 macrophage cell line. It was shown that treatment of THP-1 macrophages that are exposed to lipopolysaccharide (LPS) with CLC-loaded MAPs caused a significant (p < 0.05) reduction of TNF-α production, a pro-inflammatory cytokine typically associated with the early onset of acute gout. Accordingly, CLC-loaded MAPs could represent a new minimally-invasive alternative strategy for management of acute gout.
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Affiliation(s)
- Qonita Kurnia Anjani
- School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK. .,Fakultas Farmasi, Universitas Megarezky, Jl. Antang Raya No. 43, Makassar 90234, Indonesia
| | - Akmal Hidayat Bin Sabri
- School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK.
| | - Natalia Moreno-Castellanos
- Basic Science Department, Faculty of Health, Universidad Industrial de Santander, Bucaramanga 680001, Colombia
| | - Emilia Utomo
- School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK.
| | - Álvaro Cárcamo-Martínez
- School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK.
| | - Juan Domínguez-Robles
- School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK.
| | - Luki Ahmadi Hari Wardoyo
- Fakultas Seni Rupa dan Desain, Institut Teknologi Bandung, Jl. Ganesa No.10, Bandung 40132, Indonesia
| | - Ryan F Donnelly
- School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK.
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