Displaying publications 1 - 20 of 306 in total

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  1. Razali S, Firus Khan AY, Khatib A, Ahmed QU, Abdul Wahab R, Zakaria ZA
    Front Pharmacol, 2021;12:741683.
    PMID: 34721030 DOI: 10.3389/fphar.2021.741683
    The leaves of Neolamarckia cadamba (NC) (Roxb.) Bosser (family: Rubiaceae) are traditionally used to treat breast cancer in Malaysia; however, this traditional claim is yet to be scientifically verified. Hence, this study was aimed to evaluate the anticancer effect of NC leaves' ethanol extract against breast cancer cell line (MCF-7 cells) using an in vitro cell viability, cytotoxicity, and gene expression assays followed by the gas chromatography analysis to further confirm active principles. Results revealed 0.2 mg/ml as the half maximal inhibitory concentration (IC50) against MCF-7. The extract exerted anticancer effect against MCF-7 cells in a dose- and time-dependent manner. The cell cycle assay showed that the extract arrested MCF-7 cells in the G0/G1 phase, and apoptosis was observed after 72 h by the Annexin-V assay. The gene expression assay revealed that the cell cycle arrest was associated with the downregulation of CDK2 and subsequent upregulation of p21 and cyclin E. The extract induced apoptosis via the mediation of the mitochondrial cell death pathways. A chromatography analysis revealed the contribution of D-pinitol and myo-inositol as the two major bioactive compounds to the activity observed. Overall, the study demonstrated that NC leaves' ethanol extract exerts anticancer effect against MCF-7 human breast cancer cells through the induction of apoptosis and cell cycle arrest, thereby justifying its traditional use for the treatment of breast cancer in Malaysia.
  2. Hisamuddin ASB, Naomi R, Bin Manan KA, Bahari H, Yazid MD, Othman F, et al.
    Front Pharmacol, 2023;14:1132087.
    PMID: 37077809 DOI: 10.3389/fphar.2023.1132087
    This study assessed the toxicity of lutein-rich purple sweet potato leaf (PSPL) extract in male Sprague-Dawley rats. Methods and study design: A total of 54 adult male Sprague-Dawley rats were used. For the acute toxicity study, three rats in the acute control group were fed 2,000 mg/kg of PSPL for 14 days. The subacute toxicity study included six rats each in four groups administered 50, 250, 500, or 1,000 mg/kg for 28 days and observed for further 14 days without treatment in the subacute control and subacute satellite groups. Changes in body weight; blood biochemistry; hematological parameters; relative organ weight; and histological sections of the heart, kidney, liver, pancreas, aorta, and retina were observed for signs of toxicity. Results: The gradual increase in weekly body weight, normal level full blood count, normal liver and kidney profile, relative organ weight, and histological sections of all stained organ tissue in the treated group compared with the acute, subacute, and satellite control groups demonstrated the absence of signs of toxicity. Conclusion: Lutein-rich PSPL extract shows no signs of toxicity up to 2,000 mg/kg/day.
  3. Hisamuddin ASB, Naomi R, Manan KAB, Bahari H, Othman F, Embong H, et al.
    Front Pharmacol, 2023;14:1175907.
    PMID: 37274105 DOI: 10.3389/fphar.2023.1175907
    The objective of this study is to access the effect of purple sweet potato leaf (PSPL) extract on diabetic retinopathy (DR) of streptozotocin (STZ)-induced male Sprague-Dawley (SD) rats. In this study, rats were injected intraperitoneally with a single dose of 60 mg/kg STZ, and diabetes was confirmed on day 7. Rats were further divided into a few groups, which were then orally administered with one of the following treatments: 25 mg/kg of gliclazide (D25G), 200 mg/kg of PSPL extract (DT 200), and 400 mg/kg of PSPL extract (DT 400). However, the normal control (NS) and control group for diabetic (DNS) were given normal saline (NS) for 12 weeks. The results show that the treated group demonstrated a reduction in serum oral glucose tolerance test (OGTT) levels of DT 200 and DT 400, and an increase in the serum and retinal insulin levels, and restored oxidative stress markers in serum and retina on week 12. The PSPL extract exhibited protective effects in maintaining the kidney, liver, retina, and pancreas architecture in 400 mg/kg compared to the 200 mg/kg treated group and D25G, thereby restoring fully transparent lenses in diabetes-induced rats. In conclusion, 400 mg/kg PSPL is the most effective dose for the amelioration of STZ-induced DR pathology in male SD rats.
  4. Abbasi SH, Aftab RA, Lai PSM, Lim SK, Zainol Abidin RN
    Front Pharmacol, 2021;12:707511.
    PMID: 34447309 DOI: 10.3389/fphar.2021.707511
    Background: Due to frequent hospitalizations, complex dialysis procedures and immune compromising effects of end stage renal disease (ESRD), patients on dialysis are more prone to healthcare associated infections (HCAIs). Objective: To study the impact of HCAIs on survival and treatment outcomes among ESRD patients on renal replacement therapy (RRT). Methodology: A multicenter, retrospective study was conducted from June to December 2019 at two public hospitals of Malaysia. ESRD patients with minimum of 6 months on RRT were included, while pregnant patients and patients <18 years were excluded. Multinomial logistic regression was performed to identify risk factors associated with unsuccessful treatment outcomes. Kaplan Meier analysis was performed to study the survival. Results: A total of 670 records were examined, of which 400 patients were included as per the inclusion criteria. The mean survival time of patients without HCAIs [22.7 (95%CI:22.1-23.2)] was higher than the patients with HCAIs [19.9 (95%CI:18.8-20.9)]. Poor survival was seen in patients with >2 comorbidities, >60 years of age, low hemoglobin concentration and high C-reactive protein levels. The most frequent treatment outcome was cured [113 (64.9%)], followed by death [37 (21.3%)] and treatment failure [17 (9.8%)]. Advancing age, and low hemoglobin concentration were independent risk factors associated with death, while recurrent HCAIs, use of central venous catheters, and low serum sodium levels were risk factors for treatment failure. Conclusion: The high burden of HCAIs is a profound challenge faced by patients on RRT, which not only effects the treatment outcomes but also contributes substantially to the poor survival among these patients.
  5. Ramalingam A, Budin SB, Mohd Fauzi N, Ritchie RH, Zainalabidin S
    Front Pharmacol, 2019;10:1493.
    PMID: 31920673 DOI: 10.3389/fphar.2019.01493
    Increased exposure to nicotine contributes to the development of cardiac dysfunction by promoting oxidative stress, fibrosis, and inflammation. These deleterious events altogether render cardiac myocytes more susceptible to acute cardiac insults such as ischemia-reperfusion (I/R) injury. This study sought to elucidate the role of angiotensin II type I (AT1) receptors in cardiac injury resulting from prolonged nicotine administration in a rat model. Male Sprague-Dawley rats were given nicotine (0.6 mg/kg ip) for 28 days to induce cardiac dysfunction, alone or in combination with the AT1 receptor antagonist, irbesartan (10 mg/kg, po). Vehicle-treated rats were used as controls. Rat hearts isolated from each experimental group at study endpoint were examined for changes in function, histology, gene expression, and susceptibility against acute I/R injury determined ex vivo. Rats administered nicotine alone exhibited significantly increased cardiac expression of angiotensin II and angiotensin-converting enzyme (ACE) in addition to elevated systolic blood pressure (SBP) and heart rate. Furthermore, nicotine administration markedly reduced left ventricular (LV) performance with concomitant increases in myocardial oxidative stress, fibrosis, and inflammation. Concomitant treatment with irbesartan attenuated these effects, lowering blood pressure, heart rate, oxidative stress, and expression of fibrotic and inflammatory genes. Importantly, the irbesartan-treated group also manifested reduced susceptibility to I/R injury ex vivo. These findings suggest that AT1 receptors play an important role in nicotine-induced cardiac dysfunction, and pharmacological approaches targeting cardiac AT1 receptors may thus benefit patients with sustained exposure to nicotine.
  6. Hamid HA, Ramli AN, Yusoff MM
    Front Pharmacol, 2017;8:96.
    PMID: 28293192 DOI: 10.3389/fphar.2017.00096
    Depression is the most common illness observed in the elderly, adults, and children. Antidepressants prescribed are usually synthetic drugs and these can sometimes cause a wide range of unpleasant side effects. Current research is focussed on natural products from plants as they are a rich source of potent new drug leads. Besides Hypericum perforatum (St. John's wort), the plants studied include Passiflora incarnata L. (passion flower), Mitragyna speciosa (kratom), Piper methysticum G. Forst (kava) and Valeriana officinalis L. Harman, harmol, harmine, harmalol and harmaline are indole alkaloids isolated from P. incarnata, while mitragynine is isolated from M. speciosa. The structure of isolated compounds from P. methysticum G. Forst and V. officinalis L. contains an indole moiety. The indole moiety is related to the neurotransmitter serotonin which is widely implicated for brain function and cognition as the endogenous receptor agonist. An imbalance in serotonin levels may influence mood in a way that leads to depression. The moiety is present in a number of antidepressants already on the market. Hence, the objective of this review is to discuss bioactive compounds containing the indole moiety from plants that can serve as potent antidepressants.
  7. Ferdous UT, Yusof ZNB
    Front Pharmacol, 2021;12:593116.
    PMID: 33746748 DOI: 10.3389/fphar.2021.593116
    Though cancer therapeutics can successfully eradicate cancerous cells, the effectiveness of these medications is mostly restricted to several deleterious side effects. Therefore, to alleviate these side effects, antioxidant supplementation is often warranted, reducing reactive species levels and mitigating persistent oxidative damage. Thus, it can impede the growth of cancer cells while protecting the normal cells simultaneously. Moreover, antioxidant supplementation alone or in combination with chemotherapeutics hinders further tumor development, prevents chemoresistance by improving the response to chemotherapy drugs, and enhances cancer patients' quality of life by alleviating side effects. Preclinical and clinical studies have been revealed the efficacy of using phytochemical and dietary antioxidants from different sources in treating chemo and radiation therapy-induced toxicities and enhancing treatment effectiveness. In this context, algae, both micro and macro, can be considered as alternative natural sources of antioxidants. Algae possess antioxidants from diverse groups, which can be exploited in the pharmaceutical industry. Despite having nutritional benefits, investigation and utilization of algal antioxidants are still in their infancy. This review article summarizes the prospective anticancer effect of twenty-three antioxidants from microalgae and their potential mechanism of action in cancer cells, as well as usage in cancer therapy. In addition, antioxidants from seaweeds, especially from edible species, are outlined, as well.
  8. Hanapi NA, Chear NJ, Azizi J, Yusof SR
    Front Pharmacol, 2021;12:751656.
    PMID: 34867362 DOI: 10.3389/fphar.2021.751656
    Parallel to the growing use of kratom, there is a wealth of evidence from self-report, preclinical, and early clinical studies on therapeutic benefits of its alkaloids in particular for treating pain, managing substance use disorder, and coping with emotional or mental health conditions. On the other hand, there are also reports on potential health risks concerning kratom use. These two aspects are often discussed in reviews on kratom. Here, we aim to highlight specific areas that are of importance to give insights into the mechanistic of kratom alkaloids pharmacological actions. This includes their interactions with drug-metabolizing enzymes and predictions of clinical drug-drug interactions, receptor-binding properties, interactions with cellular barriers in regards to barrier permeability, involvement of membrane transporters, and alteration of barrier function when exposed to the alkaloids.
  9. Liu J, Zhang Y, Wu B, Wang S, Bin-Chia Wu D, You R
    Front Pharmacol, 2021;12:717504.
    PMID: 34721016 DOI: 10.3389/fphar.2021.717504
    Objectives: Baseline presence of nonstructural protein 5A (NS5A) resistance-associated variants can attenuate the efficacy of new direct-acting antivirals. A potential method to attain the higher efficacy would be to screen for NS5A polymorphisms prior to the initiation of therapy and to adjust the treatment length based on the test results. However, baseline testing adds additional costs and it is unclear whether this would represent a high value strategy for chronic hepatitis C in China. Methods: A hybrid model compared 1) standard 12-weeks treatment (no testing), 2) shortened 8-weeks treatment (no testing), and 3) baseline testing with 12-/8-weeks treatment for those with/without NS5A polymorphisms from a lifetime Chinese health care payer perspective. All model inputs were retrieved from clinical trials and publically available literature. And sensitivity analyses were also conducted to assess the impact of uncertainty. Results: Baseline testing was associated with overall increase in total health care cost of USD 13.50 and in QALYs of 0.002 compared with standard 12-weeks treatment (no testing), yielded in an ICER of USD 6750/QALY gained. Scenario analyses suggested that shortened 8-weeks treatment (no testing) was found to be lower costs and great QALYs compared with other two strategies when the sustained virologic response (SVR) rate increased to 95%. Sensitivity analyses indicated that the results were robust. Conclusions: Our results suggest prior assessment of NS5A sensitivity followed by optimizing treatment duration was an economic strategy. In addition, shortened 8-weeks treatment (no testing) was shown to be dominant with the SVR rate increased to 95%.
  10. Sayaf AM, Ullah Khalid S, Hameed JA, Alshammari A, Khan A, Mohammad A, et al.
    Front Pharmacol, 2023;14:1202128.
    PMID: 37670941 DOI: 10.3389/fphar.2023.1202128
    Introduction: Hypoxia-inducible factor (HIF) prolyl hydroxylase domain (PHD) enzymes are major therapeutic targets of anemia and ischemic/hypoxia diseases. To overcome safety issues, liver failure, and problems associated with on-/off-targets, natural products due to their novel and unique structures offer promising alternatives as drug targets. Methods: In the current study, the Marine Natural Products, North African, South African, East African, and North-East African chemical space was explored for HIF-PHD inhibitors discovery through molecular search, and the final hits were validated using molecular simulation and free energy calculation approaches. Results: Our results revealed that CMNPD13808 with a docking score of -8.690 kcal/mol, CID15081178 with a docking score of -8.027 kcal/mol, CID71496944 with a docking score of -8.48 kcal/mol and CID11821407 with a docking score of -7.78 kcal/mol possess stronger activity than the control N-[(4-hydroxy-8-iodoisoquinolin-3-yl)carbonyl]glycine, 4HG (-6.87 kcal/mol). Interaction analysis revealed that the target compounds interact with Gln239, Tyr310, Tyr329, Arg383 and Trp389 residues, and chelate the active site iron in a bidentate manner in PHD2. Molecular simulation revealed that these target hits robustly block the PHD2 active site by demonstrating stable dynamics. Furthermore, the half-life of the Arg383 hydrogen bond with the target ligands, which is an important factor for PHD2 inhibition, remained almost constant in all the complexes during the simulation. Finally, the total binding free energy of each complex was calculated as CMNPD13808-PHD2 -72.91 kcal/mol, CID15081178-PHD2 -65.55 kcal/mol, CID71496944-PHD2 -68.47 kcal/mol, and CID11821407-PHD2 -62.06 kcal/mol, respectively. Conclusion: The results show the compounds possess good activity in contrast to the control drug (4HG) and need further in vitro and in vivo validation for possible usage as potential drugs against HIF-PHD2-associated diseases.
  11. Xi S, Li Y, Yue L, Gong Y, Qian L, Liang T, et al.
    Front Pharmacol, 2020;11:582322.
    PMID: 33192523 DOI: 10.3389/fphar.2020.582322
    Viral pneumonia is one kind of acute respiratory tract infection caused by the virus. There have been many outbreaks of viral pneumonia with high contagiousness and mortality both in China and abroad, such as the great influenza in 1918, the severe acute respiratory syndrome (SARS) coronavirus in 2003, the Influenza A (H1N1) virus in 2009, and the Middle East Respiratory Syndrome coronavirus (MERS-CoV) in 2012 and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019. These outbreaks and/or pandemic have significant impact on human life, social behaviors, and economic development. Moreover, no specific drug has been developed for these viruses. Traditional Chinese medicine (TCM) plays an important role in the treatment of viral pneumonia during these outbreaks especially in SARS and SARS-CoV-2 because studies suggest that TCM formulations may target several aspects of the disease and may have lesser side effects than manufactured pharmaceuticals. In recent years, a lot of clinicians and researchers have made a series of in-depth explorations and investigations on the treatment of viral pneumonia with TCM, which have understood TCM therapeutic mechanisms more specifically and clearly. But critical analysis of this research in addition to further studies are needed to assess the potential of TCM in the treatment of viral pneumonia.
  12. Ooi BK, Chan KG, Goh BH, Yap WH
    Front Pharmacol, 2018;9:1308.
    PMID: 30498447 DOI: 10.3389/fphar.2018.01308
    Cardiovascular diseases (CVDs) are closely linked to cellular oxidative stress and inflammation. This may be resulted from the imbalance generation of reactive oxygen species and its role in promoting inflammation, thereby contributing to endothelial dysfunction and cardiovascular complications. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that plays a significant role in regulating expression of antioxidant and cytoprotective enzymes in response to oxidative stress. Natural products have emerged as a potential source of bioactive compounds which have shown to protect against atherogenesis development by activating Nrf2 signaling. This review aims to provide a comprehensive summary of the published data on the function, regulation and activation of Nrf2 as well as the molecular mechanisms of natural products in regulating Nrf2 signaling. The beneficial effects of using natural bioactive compounds as a promising therapeutic approach for the prevention and treatment of CVDs are reviewed.
  13. Sun Z, He G, Huang N, Thilakavathy K, Lim JCW, Kumar SS, et al.
    Front Pharmacol, 2021;12:707205.
    PMID: 34305613 DOI: 10.3389/fphar.2021.707205
    The total number of cumulative cases and deaths from the COVID-19 pandemic caused by SARS-CoV-2 is still increasing worldwide. Although many countries have actively implemented vaccination strategies to curb the epidemic, there is no specific efficient therapeutic drug for this virus to effectively reduce deaths. Therefore, the underappreciated macromolecular compounds have become the spotlight of research. Furthermore, the medicinal compounds in plants that provide myriad possibilities to treat human diseases have become of utmost importance. Experience indicates that Traditional Chinese medicine effectively treats SARS and has been used for treating patients with COVID-19 in China. As one of the world's oldest herbal remedies, licorice is used for treating patients with all stages of COVID-19. Glycyrrhizic acid (GA), the main active compound in licorice, has been proven effective in killing the SARS virus. Meanwhile, as a natural plant molecule, GA can also directly target important protein structures of the SARS-CoV-2 virus and inhibit the replication of SARS-CoV-2. In this review, we summarized the immune synergy of GA and its potential role in treating COVID-19 complications. Besides, we reviewed its anti-inflammatory effects on the immune system and its positive effects in cooperation with various drugs to fight against COVID-19 and its comorbidities. The purpose of this review is to elucidate and suggest that GA can be used as a potential drug during COVID-19 treatment.
  14. Lum PT, Sekar M, Seow LJ, Shaikh MF, Arulsamy A, Retinasamy T, et al.
    Front Pharmacol, 2023;14:1189957.
    PMID: 37521470 DOI: 10.3389/fphar.2023.1189957
    Huntington's disease (HD), a neurodegenerative disease, normally starts in the prime of adult life, followed by a gradual occurrence of psychiatric disturbances, cognitive and motor dysfunction. The daily performances and life quality of HD patients have been severely interfered by these clinical signs and symptoms until the last stage of neuronal cell death. To the best of our knowledge, no treatment is available to completely mitigate the progression of HD. Mangiferin, a naturally occurring potent glucoxilxanthone, is mainly isolated from the Mangifera indica plant. Considerable studies have confirmed the medicinal benefits of mangiferin against memory and cognitive impairment in neurodegenerative experimental models such as Alzheimer's and Parkinson's diseases. Therefore, this study aims to evaluate the neuroprotective effect of mangiferin against 3-nitropropionic acid (3-NP) induced HD in rat models. Adult Wistar rats (n = 32) were randomly allocated equally into four groups of eight rats each: normal control (Group I), disease control (Group II) and two treatment groups (Group III and Group IV). Treatment with mangiferin (10 and 20 mg/kg, p. o.) was given for 14 days, whereas 3-NP (15 mg/kg, i. p.) was given for 7 days to induce HD-like symptoms in rats. Rats were assessed for cognitive functions and motor coordination using open field test (OFT), novel object recognition (NOR) test, neurological assessment, rotarod and grip strength tests. Biochemical parameters such as oxidative stress markers and pro-inflammatory markers in brain hippocampus, striatum and cortex regions were evaluated. Histopathological study on brain tissue was also conducted using hematoxylin and eosin (H&E) staining. 3-NP triggered anxiety, decreased recognition memory, reduced locomotor activity, lower neurological scoring, declined rotarod performance and grip strength were alleviated by mangiferin treatment. Further, a significant depletion in brain malondialdehyde (MDA) level, an increase in reduced glutathione (GSH) level, succinate dehydrogenase (SDH), superoxide dismutase (SOD) and catalase (CAT) activities, and a decrease in tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) levels were observed in mangiferin treated groups. Mangiferin also mitigated 3-NP induced histopathological alteration in the brain hippocampus, striatum and cortex sections. It could be inferred that mangiferin protects the brain against oxidative damage and neuroinflammation, notably via antioxidant and anti-inflammatory activities. Mangiferin, which has a good safety profile, may be an alternate treatment option for treating HD and other neurodegenerative disorders. The results of the current research of mangiferin will open up new avenues for the development of safe and effective therapeutic agents in diminishing HD.
  15. Liu BH, Chong FL, Yuan CC, Liu YL, Yang HM, Wang WW, et al.
    Front Pharmacol, 2020;11:586725.
    PMID: 33708111 DOI: 10.3389/fphar.2020.586725
    Background: Recently, chronic kidney disease (CKD)-mineral and bone disorder (MBD) has become one of common complications occurring in CKD patients. Therefore, development of a new treatment for CKD-MBD is very important in the clinic. In China, Fucoidan (FPS), a natural compound of Laminaria japonica has been frequently used to improve renal dysfunction in CKD. However, it remains elusive whether FPS can ameliorate CKD-MBD. FGF23-Klotho signaling axis is reported to be useful for regulating mineral and bone metabolic disorder in CKD-MBD. This study thereby aimed to clarify therapeutic effects of FPS in the CKD-MBD model rats and its underlying mechanisms in vivo and in vitro, compared to Calcitriol (CTR). Methods: All male rats were divided into four groups: Sham, CKD-MBD, FPS and CTR. The CKD-MBD rat models were induced by adenine administration and uninephrectomy, and received either FPS or CTR or vehicle after induction of renal injury for 21 days. The changes in parameters related to renal dysfunction and renal tubulointerstitial damage, calcium-phosphorus metabolic disorder and bone lesion were analyzed, respectively. Furthermore, at sacrifice, the kidneys and bone were isolated for histomorphometry, immunohistochemistry and Western blot. In vitro, the murine NRK-52E cells were used to investigate regulative actions of FPS or CTR on FGF23-Klotho signaling axis, ERK1/2-SGK1-NHERF-1-NaPi-2a pathway and Klotho deficiency. Results: Using the modified CKD-MBD rat model and the cultured NRK-52E cells, we indicated that FPS and CTR alleviated renal dysfunction and renal tubulointerstitial damage, improved calcium-phosphorus metabolic disorder and bone lesion, and regulated FGF23-Klotho signaling axis and ERK1/2-SGK1-NHERF-1-NaPi-2a pathway in the kidney. In addition, using the shRNA-Klotho plasmid-transfected cells, we also detected, FPS accurately activated ERK1/2-SGK1-NHERF-1-NaPi-2a pathway through Klotho loss reversal. Conclusion: In this study, we emphatically demonstrated that FPS, a natural anti-renal dysfunction drug, similar to CTR, improves renal injury-related calcium-phosphorus metabolic disorder and bone abnormality in the CKD-MBD model rats. More importantly, we firstly found that beneficial effects in vivo and in vitro of FPS on phosphorus reabsorption are closely associated with regulation of FGF23-Klotho signaling axis and ERK1/2-SGK1-NHERF-1-NaPi-2a pathway in the kidney. This study provided pharmacological evidences that FPS directly contributes to the treatment of CKD-MBD.
  16. Gangwal A, Ansari A, Ahmad I, Azad AK, Kumarasamy V, Subramaniyan V, et al.
    Front Pharmacol, 2024;15:1331062.
    PMID: 38384298 DOI: 10.3389/fphar.2024.1331062
    There are two main ways to discover or design small drug molecules. The first involves fine-tuning existing molecules or commercially successful drugs through quantitative structure-activity relationships and virtual screening. The second approach involves generating new molecules through de novo drug design or inverse quantitative structure-activity relationship. Both methods aim to get a drug molecule with the best pharmacokinetic and pharmacodynamic profiles. However, bringing a new drug to market is an expensive and time-consuming endeavor, with the average cost being estimated at around $2.5 billion. One of the biggest challenges is screening the vast number of potential drug candidates to find one that is both safe and effective. The development of artificial intelligence in recent years has been phenomenal, ushering in a revolution in many fields. The field of pharmaceutical sciences has also significantly benefited from multiple applications of artificial intelligence, especially drug discovery projects. Artificial intelligence models are finding use in molecular property prediction, molecule generation, virtual screening, synthesis planning, repurposing, among others. Lately, generative artificial intelligence has gained popularity across domains for its ability to generate entirely new data, such as images, sentences, audios, videos, novel chemical molecules, etc. Generative artificial intelligence has also delivered promising results in drug discovery and development. This review article delves into the fundamentals and framework of various generative artificial intelligence models in the context of drug discovery via de novo drug design approach. Various basic and advanced models have been discussed, along with their recent applications. The review also explores recent examples and advances in the generative artificial intelligence approach, as well as the challenges and ongoing efforts to fully harness the potential of generative artificial intelligence in generating novel drug molecules in a faster and more affordable manner. Some clinical-level assets generated form generative artificial intelligence have also been discussed in this review to show the ever-increasing application of artificial intelligence in drug discovery through commercial partnerships.
  17. Vitamia C, Iftinan GN, Latarissa IR, Wilar G, Cahyanto A, Mohammed AFA, et al.
    Front Pharmacol, 2024;15:1353503.
    PMID: 38434698 DOI: 10.3389/fphar.2024.1353503
    Background: Recurrent Aphthous Stomatitis (RAS) is a common ulcerative disease of the oral mucosa which is characterized by pain, and recurrent lesions in the oral cavity. This condition is quite painful, causing difficulty in eating, speaking and swallowing. Topical medications have been used for this condition, but the obstacle in using topical medications is the difficulty of achieving drug effects due to saliva wash out. This problem can be overcome by film hydrogel formulation which can protect the ulcer and reduce the pain to some extent. α-mangostin is a xanthone isolated from the rind of the mangosteen fruit. One of the activities of α-mangostin is anti-inflammatory effects, which operate through the characteristic mechanism of inhibiting the inflammatory response. This protocol study aims to investigate the efficacy of an α-mangostin hydrogel film with a chitosan alginate base for recurrent aphthous stomatitis (RAS) in comparison with a placebo over a period of 7 days. Study design: This is a two-arm, double blinding, randomized controlled trial enrolling patients with RAS. The efficacy test of α-mangostin Hydrogel Film will be tested against the placebo. Patients with RAS will be allocated randomly into the two arms and the hydrogel film will be administered for 7 days. The diameter of ulcer and visual analog scale (VAS) score will be used as the primary efficacy endpoint. The outcome measure will be compared between the two arms at the baseline, day 3, day 5, and at the end of 7 days. Discussion: The purpose of this clinical research is to provide scientific evidence on the efficacy of α-mangostin hydrogel film with a chitosan alginate basis in treating recurrent aphthous stomatitis. The trial is expected to improve our capacity to scientifically confirm the anti-inflammatory effectiveness of α-mangostin compounds in a final formulation that is ready to use. Trial registration: NCT06039774 (14 September 2023).
  18. Bao R, Liu M, Wang D, Wen S, Yu H, Zhong Y, et al.
    Front Pharmacol, 2019;10:1464.
    PMID: 31920654 DOI: 10.3389/fphar.2019.01464
    Background:Eurycoma longifolia is a tropical medicinal plant belonging to Simaroubaceae distributed in South East Asia. The stems are traditionally used for the treatment of sexual insufficiency, fever, hypertension, and malaria. Furthermore, it has antidiabetic and anticancer activities. Recently, it has been reported to reduce uric acid, but the mechanism is unclear. Hypothesis/Purpose: The aim of this study is to explore the effect and mechanism of E. longifolia stem 70% ethanol extract (EL) and its active compounds on uric acid excretion. Study Design and Methods: Potassium oxonate (PO) induced hyperuricemia rats model and adenine-PO induced hyperuricemia mice model were used to evaluate the effects of EL. Ultraperformance liquid chromatography was used to determine the levels of plasma or serum uric acid and creatinine. Hematoxylin-eosin staining was applied to observe kidney pathological changes, and western blot was applied to detect protein expression levels of uric acid transporters. Effects of constituents on urate uptake were tested in hURAT1-expressing HEK293T cells. Results: EL significantly reduced serum and plasma uric acid levels at dosages of 100, 200, and 400 mg/kg in hyperuricemia rats and mice, increased the clearance rate of uric acid and creatinine, and improved the renal pathological injury. The protein expression levels of urate reabsorption transporter 1 (URAT1) and glucose transporter 9 were down-regulated, while sodium-dependent phosphate transporter 1 and ATP-binding cassette transporter G2 were up-regulated in the kidney after EL treatment. The quassinoids isolated from EL showed inhibitory effects on urate uptake in hURAT1-expressing HEK293T cells, and the effect of eurycomanol was further confirmed in vivo. Conclusion: Our findings revealed that EL significantly reduced blood uric acid levels, prevented pathological changes of kidney in PO induced hyperuricemia animal model, and improved renal urate transports. We partly clarified the mechanism was related to suppressing effect of URAT1 by quassinoid in EL. This study is the first to demonstrate that EL plays a role in hyperuricemia by promoting renal uric acid excretion.
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