Displaying publications 1 - 20 of 28 in total

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  1. Sadikan MZ, Abdul Nasir NA
    Naunyn Schmiedebergs Arch Pharmacol, 2023 Dec;396(12):3395-3406.
    PMID: 37401966 DOI: 10.1007/s00210-023-02599-y
    Diabetic retinopathy (DR) is one of the leading causes of permanent central blindness worldwide. Despite the complexity and inadequate understanding of DR pathogenesis, many of the underlying pathways are currently partially understood and may offer potential targets for future treatments. Anti-VEGF medications are currently the main medication for this problem. This article provides an overview of the established pharmacological treatments and those that are being developed to cure DR. We firstly reviewed the widely utilized approaches including pan-retinal photocoagulation therapy, anti-VEGF therapy, corticosteroid therapy, and surgical management of DR. Next, we discussed the mechanisms of action and prospective benefits of novel candidate medications. Current management are far from being a perfect treatment for DR, despite mild-term favorable efficiency and safety profiles. Pharmacological research should work toward developing longer-lasting treatments or new drug delivery systems, as well as on identifying new molecular targets in the pathogenetical mechanism for DR. In order to find a treatment that is specifically designed for each patient, it is also necessary to properly characterize patients, taking into account elements like hereditary factors and intraretinal neovascularization stages for effective utilization of drugs. The current and potential approaches for diabetic retinopathy. Image was constructed using Biorender.com.
  2. Chan ZCK, Leong KH, Kareem HS, Norazit A, Noor SM, Ariffin A
    Naunyn Schmiedebergs Arch Pharmacol, 2020 03;393(3):405-417.
    PMID: 31641820 DOI: 10.1007/s00210-019-01730-2
    The rationale of designing compounds containing a (3,4,5-trimethoxybenzyloxy) phenyl moiety is largely due to its potential antioxidant and cytotoxic activities. A previous study focused on its antioxidant mechanism, whereas in this study, we investigated the cytotoxicity of a series of 28 analogues and the mechanism of apoptosis of the most cytotoxic compound against wild-type (HCT-116) and p53 mutant (HT-29) colorectal cancer cell lines. The series of analogues comprise of different families, namely hydrazone, oxadiazole, thiosemicarbazides and triazoles. In the initial cytotoxicity screening, N-(3,4,5-trimethoxybenzylidene)-4-(3,4,5-trimethoxybenzyloxy) benzohydrazide, henceforth known as, P5H, was found to be most cytotoxic against human colorectal cancer cell lines (IC50 for HCT-116 = 11.79 μM and HT-29 = 18.52 μM). Additionally, P5H was found to have some degree of selectivity towards cancer cells compared to normal human colon cells (CCD-112 CoN). Subsequent investigation had brought insight on P5H ability to induce apoptosis in both HCT-116 and HT-29 cell lines. Cell cycle analysis showed both cell lines were arrested at the G2/M phase upon treatment. Our study concluded that P5H induced the death receptor, DR5 in HCT-116 and mitochondria-mediated apoptosis pathway in HT-29. Therefore, P5H may be a promising candidate as a chemotherapy agent against colon cancer. Graphical abstract The apoptotic pathways induced in HT-29 and HCT-116 cells upon P5H treatment.
  3. Al Batran R, Al-Bayaty F, Al-Obaidi MM, Ashrafi A
    Naunyn Schmiedebergs Arch Pharmacol, 2014 Dec;387(12):1141-52.
    PMID: 25172523 DOI: 10.1007/s00210-014-1041-x
    Atherosclerosis is the commonest and most important vascular disease. Andrographolide (AND) is the main bioactive component of the medicinal plant Andrographis paniculata and is used in traditional medicine. This study was aimed to evaluate the antiatherogenic effect of AND against atherosclerosis induced by Porphyromonas gingivalis in White New Zealand rabbits. Thirty rabbits were divided into five groups as follows: G1, normal group; G2-5, were orally challenged with P. gingivalis five times a week over 12 weeks; G2, atherogenic control group; G3, standard group treated with atorvastatin (AV) 5 mg/kg; and G4 and G5, treatment groups treated with AND 10 and 20 mg/kg, respectively over 12 weeks. Serums were subjected to antioxidant enzymatic and anti-inflammatory activities, and the aorta was subjected to histological analyses. Groups treated with AND showed a significant reversal of liver and renal biochemical changes, compared with the atherogenic control group. In the same groups, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), total glutathione (GSH) levels in serum were significantly increased (P < 0.05), and lipid peroxidation (malondialdehyde (MDA)) levels were significantly decreased (P < 0.05), respectively. Furthermore, treated groups with AV and AND showed significant decrease in the level of VCAM-1 and ICAM-1 compared with the atherogenic control group. In aortic homogenate, the level of nitrotyrosine was significantly increased, while the level of MCP1 was significantly decreased in AV and AND groups compared with the atherogenic control group. In addition, staining the aorta with Sudan IV showed a reduction in intimal thickening plaque in AV and AND groups compared with the atherogenic control group. AND has showed an antiatherogenic property as well as the capability to reduce lipid, liver, and kidney biomarkers in atherogenic serum that prevents atherosclerosis complications caused by P. gingivalis.
  4. Chaudhry GE, Zeenia, Sharifi-Rad J, Calina D
    Naunyn Schmiedebergs Arch Pharmacol, 2024 Apr;397(4):1919-1934.
    PMID: 37594522 DOI: 10.1007/s00210-023-02645-9
    Cancer is a complex disease characterized by dysregulated cell growth and division, posing significant challenges for effective treatment. Hispidulin, a flavonoid compound, has shown promising biological effects, particularly in the field of anticancer research. The main objective of this study is to investigate the anticancer properties of hispidulin and gain insight into its mechanistic targets in cancer cells. A comprehensive literature review was conducted to collect data on the anticancer effects of hispidulin. In vitro and in vivo studies were analyzed to identify the molecular targets and underlying mechanisms through which hispidulin exerts its anticancer activities. Hispidulin has shown significant effects on various aspects of cancer, including cell growth, proliferation, cell cycle regulation, angiogenesis, metastasis, and apoptosis. It has been observed to target both extrinsic and intrinsic apoptotic pathways, regulate cell cycle arrest, and modulate cancer progression pathways. The existing literature highlights the potential of hispidulin as a potent anticancer agent. Hispidulin exhibits promising potential as a therapeutic agent for cancer treatment. Its ability to induce apoptosis and modulate key molecular targets involved in cancer progression makes it a valuable candidate for further investigation. Additional pharmacological studies are needed to fully understand the specific targets and signaling pathways influenced by hispidulin in different types of cancer. Further research will contribute to the successful translation of hispidulin into clinical settings, allowing its utilization in conventional and advanced cancer therapies with improved therapeutic outcomes and reduced side effects.
  5. Siaw YM, Jeevanandam J, Hii YS, Chan YS
    Naunyn Schmiedebergs Arch Pharmacol, 2020 Dec;393(12):2253-2264.
    PMID: 32632566 DOI: 10.1007/s00210-020-01934-x
    In recent times, magnesium oxide (MgO) nanoparticles are proven to be an excellent antibacterial agent which inhibits the growth of bacteria by generating reactive oxygen species (ROS). Release of ROS by nanoparticles will damage the cell membrane of bacteria and leads to the leakage of bacterial internal components and cell death. However, chemically synthesized MgO nanoparticles may possess toxic functional groups which may inhibit healthy human cells along with bacterial cells. Thus, the aim of the present study is to synthesize MgO nanoparticles using leaf extracts of Amaranthus tricolor and photo-irradiation of visible light as a catalyst, without addition of any chemicals. Optimization was performed using Box-Behnken design (BBD) to obtain the optimum condition required to synthesize smallest nanoparticles. The parameters such as time of reaction, the concentration of precursor, and light intensity have been identified to affect the size of biosynthesized nanoparticles and was optimized. The experiment performed with optimized conditions such as 0.001 M concentration of magnesium acetate as precursor, 5 cm distance of light (intensity), and 15 min of reaction time (light exposure) has led to the formation of 74.6 nm sized MgO nanoparticles. The antibacterial activities of MgO nanoparticles formed via photo-irradiation and conventional biosynthesis approach were investigated and compared. The lethal dosage of E. coli for photo-irradiated and conventional biosynthesis MgO nanoparticles was 0.6 ml and 0.4 ml, respectively. Likewise, the lethal dosage of S. aureus for both biosynthesis approaches was found to be 0.4 ml. The results revealed that the antibacterial activity of MgO nanoparticles from both biosynthesis approaches was similar. Thus, photo-irradiated MgO nanoparticles were beneficial over heat-mediated conventional method due to the reduced synthesis duration.
  6. Kumari R, Negi M, Thakur P, Mahajan H, Raina K, Sharma R, et al.
    Naunyn Schmiedebergs Arch Pharmacol, 2024 Mar;397(3):1505-1524.
    PMID: 37755516 DOI: 10.1007/s00210-023-02694-0
    Saussurea costus (Falc.) Lipsch., commonly known as costus, is a perennial herb that has been traditionally used in various indigenous medicinal systems across Asia. Its historical prominence in traditional remedies underscores the need to explore its phytochemical composition, pharmacological properties, and potential therapeutic benefits. This review aims to provide a comprehensive overview of the available literature on the pharmacological properties, phytochemical constituents, ethnobotanical uses, and therapeutic potential of S. costus. An exhaustive search was performed across multiple electronic databases, including PubMed/MedLine, Google Scholar, Web of Science, Scopus, TRIP database, and Science Direct. Both experimental and clinical studies, as well as traditional ethnobotanical records, were considered for inclusion. The phytochemical analysis revealed that S. costus contains a plethora of bioactive compounds, including sesquiterpenes, flavonoids, and essential oils, which are responsible for its myriad of medicinal properties. The pharmacological studies have demonstrated its anti-inflammatory, anti-oxidant, anti-cancer, hepatoprotective, and immunomodulatory effects, among others. Ethnobotanical data showcased its extensive use in treating ailments like asthma, digestive disorders, and skin conditions. Some clinical trials also underscore its efficacy in certain health conditions, corroborating its traditional uses. S. costus possesses significant therapeutic potential, largely attributable to its rich phytochemical composition; the convergence of its traditional uses and modern pharmacological findings suggests promising avenues for future research, especially in drug development and understanding its mechanism of action in various ailments.
  7. Liow KY, Chow SC
    Naunyn Schmiedebergs Arch Pharmacol, 2018 Jan;391(1):71-82.
    PMID: 29085973 DOI: 10.1007/s00210-017-1436-6
    The cathepsin B inhibitor benzyloxycarbonyl-phenylalanine-alanine-chloromethyl ketone (z-FA-CMK) was recently found to induce apoptosis at low concentrations in Jurkat T cells, while at higher concentrations, the cells die of necrosis. In the present study, we showed that z-FA-CMK readily depletes intracellular glutathione (GSH) with a concomitant increase in reactive oxygen species (ROS) generation. The toxicity of z-FA-CMK in Jurkat T cells was completely abrogated by N-acetylcysteine (NAC), suggesting that the toxicity mediated by z-FA-CMK is due to oxidative stress. We found that L-buthionine sulfoximine (BSO) which depletes intracellular GSH through the inhibition of GSH biosynthesis in Jurkat T cells did not promote ROS increase or induce cell death. However, NAC was still able to block z-FA-CMK toxicity in Jurkat T cells in the presence of BSO, indicating that the protective effect of NAC does not involve GSH biosynthesis. This is further corroborated by the protective effect of the non-metabolically active D-cysteine on z-FA-CMK toxicity. Furthermore, in BSO-treated cells, z-FA-CMK-induced ROS increased which remains unchanged, suggesting that the depletion of GSH and increase in ROS generation mediated by z-FA-CMK may be two separate events. Collectively, our results demonstrated that z-FA-CMK toxicity is mediated by oxidative stress through the increase in ROS generation.
  8. Andra S, Balu SK, Jeevanandham J, Muthalagu M, Vidyavathy M, Chan YS, et al.
    Naunyn Schmiedebergs Arch Pharmacol, 2019 07;392(7):755-771.
    PMID: 31098696 DOI: 10.1007/s00210-019-01666-7
    Developments in nanotechnology field, specifically, metal oxide nanoparticles have attracted the attention of researchers due to their unique sensing, electronic, drug delivery, catalysis, optoelectronics, cosmetics, and space applications. Physicochemical methods are used to fabricate nanosized metal oxides; however, drawbacks such as high cost and toxic chemical involvement prevail. Recent researches focus on synthesizing metal oxide nanoparticles through green chemistry which helps in avoiding the involvement of toxic chemicals in the synthesis process. Bacteria, fungi, and plants are the biological sources that are utilized for the green nanoparticle synthesis. Due to drawbacks such as tedious maintenance and the time needed for the nanoparticle formation, plant extracts are widely used in nanoparticle production. In addition, plants are available all over the world and phytosynthesized nanoparticles show comparatively less toxicity towards mammalian cells. Secondary metabolites including flavonoids, terpenoids, and saponins are present in plant extracts, and these are highly responsible for nanoparticle formation and reduction of toxicity. Hence, this article gives an overview of recent developments in the phytosynthesis of metal oxide nanoparticles and their toxic analysis in various cells and animal models. Also, their possible mechanism in normal and cancer cells, pharmaceutical applications, and their efficiency in disease treatment are also discussed.
  9. De Rubis G, Paudel KR, Corrie L, Mehndiratta S, Patel VK, Kumbhar PS, et al.
    PMID: 37991539 DOI: 10.1007/s00210-023-02830-w
    Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) are among the leading causes of mortality worldwide. Cigarette smoking is among the main aetiologic factors for both ailments. These diseases share common pathogenetic mechanisms including inflammation, oxidative stress, and tissue remodelling. Current therapeutic approaches are limited by low efficacy and adverse effects. Consequentially, LC has a 5-year survival of < 20%, while COPD is incurable, underlining the necessity for innovative treatment strategies. Two promising emerging classes of therapy against these diseases include plant-derived molecules (phytoceuticals) and nucleic acid-based therapies. The clinical application of both is limited by issues including poor solubility, poor permeability, and, in the case of nucleic acids, susceptibility to enzymatic degradation, large size, and electrostatic charge density. Nanoparticle-based advanced drug delivery systems are currently being explored as flexible systems allowing to overcome these limitations. In this review, an updated summary of the most recent studies using nanoparticle-based advanced drug delivery systems to improve the delivery of nucleic acids and phytoceuticals for the treatment of LC and COPD is provided. This review highlights the enormous relevance of these delivery systems as tools that are set to facilitate the clinical application of novel categories of therapeutics with poor pharmacokinetic properties. This picture was generated with BioRender.
  10. Bhat AA, Gupta G, Goyal A, Thapa R, Almalki WH, Kazmi I, et al.
    PMID: 37917370 DOI: 10.1007/s00210-023-02809-7
    Circular RNAs (circRNAs) have emerged as pivotal regulators of gene expression and cellular processes in various physiological and pathological conditions. In recent years, there has been a growing interest in investigating the role of circRNAs in inflammatory lung diseases, owing to their potential to modulate inflammation-associated pathways and contribute to disease pathogenesis. Inflammatory lung diseases, like asthma, chronic obstructive pulmonary disease (COPD), and COVID-19, pose significant global health challenges. The dysregulation of inflammatory responses demonstrates a pivotal function in advancing these diseases. CircRNAs have been identified as important players in regulating inflammation by functioning as miRNA sponges, engaging with RNA-binding proteins, and participating in intricate ceRNA networks. These interactions enable circRNAs to regulate the manifestation of key inflammatory genes and signaling pathways. Furthermore, emerging evidence suggests that specific circRNAs are differentially expressed in response to inflammatory stimuli and exhibit distinct patterns in various lung diseases. Their involvement in immune cell activation, cytokine production, and tissue remodeling processes underscores their possible capabilities as therapeutic targets and diagnostic biomarkers. Harnessing the knowledge of circRNA-mediated regulation in inflammatory lung diseases could lead to the development of innovative strategies for disease management and intervention. This review summarizes the current understanding of the role of circRNAs in inflammatory lung diseases, focusing on their regulatory mechanisms and functional implications.
  11. Malyla V, De Rubis G, Paudel KR, Chellappan DK, Hansbro NG, Hansbro PM, et al.
    Naunyn Schmiedebergs Arch Pharmacol, 2023 Dec;396(12):3595-3603.
    PMID: 37266589 DOI: 10.1007/s00210-023-02553-y
    Lung cancer (LC) is the leading cause of cancer-related deaths globally. It accounts for more than 1.9 million cases each year due to its complex and poorly understood molecular mechanisms that result in unregulated cell proliferation and metastasis. β-Catenin is a developmentally active protein that controls cell proliferation, metastasis, polarity and cell fate during homeostasis and aids in cancer progression via epithelial-mesenchymal transition. Therefore, inhibition of the β-catenin pathway could attenuate the progression of LC. Berberine, an isoquinoline alkaloid which is known for its anti-cancer and anti-inflammatory properties, demonstrates poor solubility and bioavailability. In our study, we have encapsulated berberine into liquid crystalline nanoparticles to improve its physiochemical functions and studied if these nanoparticles target the β-catenin pathway to inhibit the human lung adenocarcinoma cell line (A549) at both gene and protein levels. We observed for the first time that berberine liquid crystalline nanoparticles at 5 µM significantly attenuate the expression of the β-catenin gene and protein. The interaction between berberine and β-catenin was further validated by molecular simulation studies. Targeting β-catenin with berberine nanoparticles represents a promising strategy for the management of lung cancer progression.
  12. Manandhar B, Paudel KR, Clarence DD, De Rubis G, Madheswaran T, Panneerselvam J, et al.
    Naunyn Schmiedebergs Arch Pharmacol, 2024 Jan;397(1):343-356.
    PMID: 37439806 DOI: 10.1007/s00210-023-02603-5
    Lung cancer is the second most prevalent type of cancer and is responsible for the highest number of cancer-related deaths worldwide. Non-small-cell lung cancer (NSCLC) makes up the majority of lung cancer cases. Zerumbone (ZER) is natural compound commonly found in the roots of Zingiber zerumbet which has recently demonstrated anti-cancer activity in both in vitro and in vivo studies. Despite their medical benefits, ZER has low aqueous solubility, poor GI absorption and oral bioavailability that hinders its effectiveness. Liquid crystalline nanoparticles (LCNs) are novel drug delivery carrier that have tuneable characteristics to enhance and ease the delivery of bioactive compounds. This study aimed to formulate ZER-loaded LCNs and investigate their effectiveness against NSCLC in vitro using A549 lung cancer cells. ZER-LCNs, prepared in the study, inhibited the proliferation and migration of A549 cells. These inhibitory effects were superior to the effects of ZER alone at a concentration 10 times lower than that of free ZER, demonstrating a potent anti-cancer activity of ZER-LCNs. The underlying mechanisms of the anti-cancer effects by ZER-LCNs were associated with the transcriptional regulation of tumor suppressor genes P53 and PTEN, and metastasis-associated gene KRT18. The protein array data showed downregulation of several proliferation associated proteins such as AXL, HER1, PGRN, and BIRC5 and metastasis-associated proteins such as DKK1, CAPG, CTSS, CTSB, CTSD, and PLAU. This study provides evidence of potential for increasing the potency and effectiveness of ZER with LCN formulation and developing ZER-LCNs as a treatment strategy for mitigation and treatment of NSCLC.
  13. Paudel KR, Clarence DD, Panth N, Manandhar B, De Rubis G, Devkota HP, et al.
    Naunyn Schmiedebergs Arch Pharmacol, 2024 Apr;397(4):2465-2483.
    PMID: 37851060 DOI: 10.1007/s00210-023-02760-7
    The purpose of this study was to evaluate the potential of zerumbone-loaded liquid crystalline nanoparticles (ZER-LCNs) in the protection of broncho-epithelial cells and alveolar macrophages against oxidative stress, inflammation and senescence induced by cigarette smoke extract in vitro. The effect of the treatment of ZER-LCNs on in vitro cell models of cigarette smoke extract (CSE)-treated mouse RAW264.7 and human BCi-NS1.1 basal epithelial cell lines was evaluated for their anti-inflammatory, antioxidant and anti-senescence activities using colorimetric and fluorescence-based assays, fluorescence imaging, RT-qPCR and proteome profiler kit. The ZER-LCNs successfully reduced the expression of pro-inflammatory markers including Il-6, Il-1β and Tnf-α, as well as the production of nitric oxide in RAW 264.7 cells. Additionally, ZER-LCNs successfully inhibited oxidative stress through reduction of reactive oxygen species (ROS) levels and regulation of genes, namely GPX2 and GCLC in BCi-NS1.1 cells. Anti-senescence activity of ZER-LCNs was also observed in BCi-NS1.1 cells, with significant reductions in the expression of SIRT1, CDKN1A and CDKN2A. This study demonstrates strong in vitro anti-inflammatory, antioxidative and anti-senescence activities of ZER-LCNs paving the path for this formulation to be translated into a promising therapeutic agent for chronic respiratory inflammatory conditions including COPD and asthma.
  14. Gulati N, Chellappan DK, MacLoughlin R, Gupta G, Singh SK, Oliver BG, et al.
    PMID: 38078921 DOI: 10.1007/s00210-023-02882-y
    Asthma, lung cancer, cystic fibrosis, tuberculosis, acute respiratory distress syndrome, chronic obstructive pulmonary disease, and COVID-19 are few examples of inflammatory lung conditions that cause cytokine release syndrome. It can initiate a widespread inflammatory response and may activate several inflammatory pathways that cause multiple organ failures leading to increased number of deaths and increased prevalence rates around the world. Nanotechnology-based therapeutic modalities such as nanoparticles, liposomes, nanosuspension, monoclonal antibodies, and vaccines can be used in the effective treatment of inflammatory lung diseases at both cellular and molecular levels. This would also help significantly in the reduction of patient mortality. Therefore, nanotechnology could be a potent platform for repurposing current medications in the treatment of inflammatory lung diseases. The aim and approach of this article are to highlight the clinical manifestations of cytokine storm in inflammatory lung diseases along with the advances and potential applications of nanotechnology-based therapeutics in the management of cytokine storm. Further in-depth studies are required to understand the molecular pathophysiology, and how nanotechnology-based therapeutics can help to effectively combat this problem.
  15. Ishak NIM, Mohamed S, Madzuki IN, Mustapha NM, Esa NM
    Naunyn Schmiedebergs Arch Pharmacol, 2021 09;394(9):1907-1915.
    PMID: 34009457 DOI: 10.1007/s00210-021-02101-6
    Inflammation and compromised immune responses often increase colorectal cancer (CRC) risk. The immune-modulating effects of limonin on carcinogen/inflammation-induced colorectal cancer (CRC) were studied in mice. Male Balb/c mice were randomly assorted into three groups (n = 6): healthy control, non-treated CRC-induced (azoxymethane/dextran-sulfate-sodium AOM/DSS) control, and CRC-induced + 50 mg limonin/kg body weight. The CRC developments were monitored via macroscopic, histopathological, ELISA, and mRNA expression analyses. Limonin downregulated inflammation (TNF-α, tumor necrosis factor-α), enhanced the adaptive immune responses (CD8, CD4, and CD19), and upregulated antioxidant defense (Nrf2, SOD2) mRNA expressions. Limonin reduced serum malondialdehyde (MDA, lipid peroxidation biomarker), prostaglandin E2, and histopathology inflammation scores, while increasing reduced glutathione (GSH) in CRC-induced mice. Limonin significantly (p 
  16. Ashique S, Garg A, Mishra N, Raina N, Ming LC, Tulli HS, et al.
    Naunyn Schmiedebergs Arch Pharmacol, 2023 Nov;396(11):2769-2792.
    PMID: 37219615 DOI: 10.1007/s00210-023-02522-5
    Lung cancer is the most common type of cancer, with over 2.1 million cases diagnosed annually worldwide. It has a high incidence and mortality rate, leading to extensive research into various treatment options, including the use of nanomaterial-based carriers for drug delivery. With regard to cancer treatment, the distinct biological and physico-chemical features of nano-structures have acquired considerable impetus as drug delivery system (DDS) for delivering medication combinations or combining diagnostics and targeted therapy. This review focuses on the use of nanomedicine-based drug delivery systems in the treatment of lung cancer, including the use of lipid, polymer, and carbon-based nanomaterials for traditional therapies such as chemotherapy, radiotherapy, and phototherapy. The review also discusses the potential of stimuli-responsive nanomaterials for drug delivery in lung cancer, and the limitations and opportunities for improving the design of nano-based materials for the treatment of non-small cell lung cancer (NSCLC).
  17. Yew KC, Tan QR, Lim PC, Low WY, Lee CY
    Naunyn Schmiedebergs Arch Pharmacol, 2024 Mar;397(3):1421-1431.
    PMID: 37728622 DOI: 10.1007/s00210-023-02716-x
    Direct-acting antivirals (DAA) have become the treatment of choice for hepatitis C. Nevertheless, efficacy of DAA in preventing hepatitis C complications remains uncertain. We evaluated the impact of DAA on hepatocellular carcinoma (HCC) occurrence and recurrence, all-cause mortality, liver decompensation and liver transplantation as compared to non-DAA treated hepatitis C and the association to baseline liver status. A systematic search for articles from March 1993 to March 2022 was conducted using three electronic databases. Randomized, case-control and cohort studies with comparison to non-DAA treatment and reporting at least one outcome were included. Meta-analysis and sub-group meta-analysis based on baseline liver status were performed. Of 1497 articles retrieved, 19 studies were included, comprising of 266,310 patients (56.07% male). DAA reduced HCC occurrence significantly in non-cirrhosis (RR 0.80, 95% CI 0.69-0.92) and cirrhosis (RR 0.39, 95% CI 0.24-0.64) but not in decompensated cirrhosis. DAA treatment lowered HCC recurrence (RR 0.71, 95% CI 0.55-0.92) especially in patients with baseline HCC and waiting for liver transplant. DAA also reduced all-cause mortality (RR 0.43, 95% CI 0.23-0.78) and liver decompensation (RR 0.52, 95% CI 0.33-0.83) significantly. However, DAA did not prevent liver transplantation. The study highlighted the importance of early DAA initiation in hepatitis C treatment for benefits beyond sustained virological response. DAA therapy prevented HCC particularly in non-cirrhosis and compensated cirrhosis groups indicating benefits in preventing further worsening of liver status. Starting DAA early also reduced HCC recurrence, liver decompensation, and all-cause mortality.
  18. Zakaria ZA, Safarul M, Valsala R, Sulaiman MR, Fatimah CA, Somchit MN, et al.
    Naunyn Schmiedebergs Arch Pharmacol, 2005 Jul;372(1):55-62.
    PMID: 16133487
    A series of preliminary studies was carried out to evaluate the antinociceptive (pain relief) activity of the aqueous extract of Corchorus olitorius L. leaves (COAE) and to determine the influence of temperature and opioid receptors on COAE activity using the abdominal constriction and hot plate tests in mice. COAE, at concentrations of 10, 25, 50, 75, and 100%, showed both peripheral and central antinociception that are non-concentration- and concentration-dependent respectively. The peripheral activity was clearly observed at a concentration of 25% and diminished at a concentration of 100%, while the central activity was observed at all the concentrations of COAE used. Furthermore, the insignificant results obtained indicated that this peripheral activity (at concentrations of 25 and 50%) was comparable to that of morphine (0.8 mg/kg). Pre-heating COAE at a temperature of 80 degrees C and 100 degrees C, or 60 degrees C and 80 degrees C was found to enhance its peripheral and central antinociception respectively. Pre-treatment with naloxone (10 mg/kg), a general opioid receptor antagonist, for 5 min, followed by COAE, was found to completely block its peripheral, but not central, antinociceptive activity. Based on this observation, we conclude that the antinociceptive activity exhibited by C. olitorius is enhanced by the increase in temperature and may be mediated peripherally, but not centrally, at least in part, via an opioid receptor.
  19. Garg P, Pundir S, Ali A, Panja S, Chellappan DK, Dua K, et al.
    PMID: 38055069 DOI: 10.1007/s00210-023-02862-2
    Moringa oleifera Lam. is a pan-tropical plant well known to the ancient world for its extensive therapeutic benefits in the Ayurvedic and Unani medical systems. The ancient world was familiar with this tree, but it has only lately been rediscovered as a multifunctional species with a huge range of possible therapeutic applications. It is a folk remedy for skin diseases, edema, sore gums, etc. This review comprises the history, ethnomedicinal applications, botanical characteristics, geographic distribution, propagation, nutritional and phytochemical profile, dermatological effects, and commercially available cosmeceuticals of Moringa oleifera Lam.Compilation of all the presented data has been done by employing various search engines like Science Direct, Google, PubMed, Research Gate, EBSCO, SciVal, SCOPUS, and Google Scholar.Studies on phytochemistry claim the presence of a variety of substances, including fatty acids, phenolic acids, sterols, oxalates, tocopherols, carotenoids, flavonoids, flavonols glycosides, tannins, terpenoids, terpene, saponins, phylates, alkaloids, glucosinolates, glycosides, and isothiocyanate. The pharmacological studies have shown the efficacy of Moringa oleifera Lam. as an antibacterial, antifungal, anti-inflammatory, antioxidant, anti-atopic dermatitis, antipsoriatic, promoter of wound healing, effective in treating herpes simplex virus, photoprotective, and UV protective. As a moisturizer, conditioner, hair growth promoter, cleanser, antiwrinkle, anti-aging, anti-acne, scar removal, pigmentation, and control for skin infection, sores, as well as sweating, it has also been utilized in a range of cosmeceuticals.he Moringa oleifera Lam. due to its broad range of phytochemicals can be proven boon for the treatment of dermatological disorders.
  20. Pang CY, Mak JW, Ismail R, Ong CE
    Naunyn Schmiedebergs Arch Pharmacol, 2012 May;385(5):495-502.
    PMID: 22307090 DOI: 10.1007/s00210-012-0731-5
    The inhibitory effects of five flavonoids with distinct chemical classes (flavones [luteolin], flavonols [quercetin and quercitrin], and flavanones [hesperetin and hespiridin]) on cDNA-expressed CYP2C8 were investigated. CYP2C8 was co-expressed with NADPH-cytochrome P450 reductase in Escherichia coli and used to characterise potency and mechanism of these flavonoids on the isoform. Tolbutamide 4-methylhydroxylase, a high-performance liquid chromatography-based assay, was selected as marker activity for CYP2C8. Our results indicated that the flavonoids inhibited CYP2C8 with different potency. The order of inhibitory activities was quercetin > luteolin > hesperetin > hesperidin > quercitrin. All of these compounds however exhibited mechanism-based inhibition. A number of structural factors were found to be important for inhibition; these include the molecular shape (volume to surface ratio), the number of hydroxyl groups as well as glycosylation of the hydroxyl group. Quercetin was the most potent inhibitor among the flavonoids examined in this study, and our data suggest that it should be examined for potential pharmacokinetic drug interactions pertaining to CYP2C8 substrates in vivo.
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