Displaying publications 61 - 80 of 167 in total

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  1. Tan HL, Chan KG, Pusparajah P, Saokaew S, Duangjai A, Lee LH, et al.
    Front Pharmacol, 2016;7:191.
    PMID: 27445824 DOI: 10.3389/fphar.2016.00191
    Epimedium (family Berberidaceae), commonly known as Horny Goat Weed or Yin Yang Huo, is commonly used as a tonic, aphrodisiac, anti-rheumatic and anti-cancer agent in traditional herbal formulations in Asian countries such as China, Japan, and Korea. The major bioactive compounds present within this plant include icariin, icaritin and icariside II. Although it is best known for its aphrodisiac properties, scientific and pharmacological studies suggest it possesses broad therapeutic capabilities, especially for enhancing reproductive function and osteoprotective, neuroprotective, cardioprotective, anti-inflammatory and immunoprotective effects. In recent years, there has been great interest in scientific investigation of the purported anti-cancer properties of icariin and its derivatives. Data from in vitro and in vivo studies suggests these compounds demonstrate anti-cancer activity against a wide range of cancer cells which occurs through various mechanisms such as apoptosis, cell cycle modulation, anti-angiogenesis, anti-metastasis and immunomodulation. Of note, they are efficient at targeting cancer stem cells and drug-resistant cancer cells. These are highly desirable properties to be emulated in the development of novel anti-cancer drugs in combatting the emergence of drug resistance and overcoming the limited efficacy of current standard treatment. This review aims to summarize the anti-cancer mechanisms of icariin and its derivatives with reference to the published literature. The currently utilized applications of icariin and its derivatives in cancer treatment are explored with reference to existing patents. Based on the data compiled, icariin and its derivatives are shown to be compounds with tremendous potential for the development of new anti-cancer drugs.
  2. Letchumanan V, Chan KG, Khan TM, Bukhari SI, Ab Mutalib NS, Goh BH, et al.
    Front Microbiol, 2017;8:728.
    PMID: 28484445 DOI: 10.3389/fmicb.2017.00728
    Bacteria must develop resistance to various inhospitable conditions in order to survive in the human gastrointestinal tract. Bile, which is secreted by the liver, and plays an important role in food digestion also has antimicrobial properties and is able to disrupt cellular homeostasis. Paradoxically, although bile is one of the guts defenses, many studies have reported that bacteria such as Vibrio parahaemolyticus can sense bile and use its presence as an environmental cue to upregulate virulence genes during infection. This article aims to discuss how bile is detected by V. parahaemolyticus and its role in regulating type III secretion system 2 leading to human infection. This bile-bacteria interaction pathway gives us a clearer understanding of the biochemical and structural analysis of the bacterial receptors involved in mediating a response to bile salts which appear to be a significant environmental cue during initiation of an infection.
  3. Khan TM, Wu DB, Goh BH, Lee LH, Alhafez AA, Syed Sulaiman SA
    Sci Rep, 2016 11 08;6:36555.
    PMID: 27824127 DOI: 10.1038/srep36555
    A prospective, observational, longitudinal study was conducted to assess the effectiveness of 75 mg pregabalin (PG) post-hemodialysis (pHD) for treatment-resistant uremic pruritus (UP). A total of forty-five patients completed the entire six week follow-up. At the baseline assessment, the majority of the patients were distressed by the UP frequency and intensity. Sleep (mean = 3.30 ± 1.1), leisure/social activities (mean = 2.90 ± 0.80) and distribution (mean = 2.92 ± 0.34) were the three domains that were primarily effected by the UP. Overall, further reduction in the 5D-itching scale (IS) was noted at day 42, which confirmed a sustained (B = -12.729, CI -13.257 to -12.201, p 
  4. Bukhsh A, Khan TM, Lee SWH, Lee LH, Chan KG, Goh BH
    Front Pharmacol, 2018;9:339.
    PMID: 29692730 DOI: 10.3389/fphar.2018.00339
    Background: Comparative efficacy of different pharmacist based interventions on glycemic control of type 2 diabetes patients is unclear. This review aimed to evaluate and compare the efficacy of different pharmacist based interventions on clinical outcomes of type 2 diabetes patients. Methods: A systematic search was conducted across five databases from date of database inception to September 2017. All randomized clinical trials evaluating the efficacy of pharmacist based interventions on type 2 diabetes patients were included for network meta-analysis (NMA). The protocol is available with PROSPERO (CRD42017078854). Results: A total of 43 studies, involving 6259 type 2 diabetes patients, were included. NMA demonstrated that all interventions significantly lowered glycosylated hemoglobin (HbA1c) levels compared to usual care, but there was no statistical evidence from this study that one intervention was significantly better than the other for reducing HbA1c levels. Pharmacist based diabetes education plus pharmaceutical care showed maximum efficacy for reducing HbA1c levels [-0.86, 95% CI -0.983, -0.727; p < 0.001]. Pharmacist based diabetes education plus pharmaceutical care was observed to be statistically significant in lowering levels of systolic blood pressure [-4.94; 95%CI -8.65, -1.23] and triglycerides levels [-0.26, 95%CI -0.51, -0.01], as compared to the interventions which involved diabetes education by pharmacist, and for body mass index (BMI) [-0.57; 95%CI -1.25, -0.12] in comparison to diabetes education by health care team involving pharmacist as member. Conclusion: The findings of this review demonstrate that all interventions had a significantly positive effect on HbA1c, but there was no statistical evidence from this study that one intervention was significantly better than the other for achieving glycemic control.Pharmacist based diabetes education plus pharmaceutical care showed maximum efficacy on HbA1c and rest of the clinical outcomes.
  5. Tan LT, Chan KG, Chan CK, Khan TM, Lee LH, Goh BH
    Biomed Res Int, 2018;2018:4823126.
    PMID: 29805975 DOI: 10.1155/2018/4823126
    Mangrove derived microorganisms constitute a rich bioresource for bioprospecting of bioactive natural products. This study explored the antioxidant potentials of Streptomyces bacteria derived from mangrove soil. Based on 16S rRNA phylogenetic analysis, strain MUM292 was identified as the genus Streptomyces. Strain MUM292 showed the highest 16S rRNA gene sequence similarity of 99.54% with S. griseoruber NBRC12873T. Furthermore, strain MUM292 was also characterized and showed phenotypic characteristics consistent with Streptomyces bacteria. Fermentation and extraction were performed to obtain the MUM292 extract containing the secondary metabolites of strain MUM292. The extract displayed promising antioxidant activities, including DPPH, ABTS, and superoxide radical scavenging and also metal-chelating activities. The process of lipid peroxidation in lipid-rich product was also retarded by MUM292 extract and resulted in reduced MDA production. The potential bioactive constituents of MUM292 extract were investigated using GC-MS and preliminary detection showed the presence of pyrazine, pyrrole, cyclic dipeptides, and phenolic compound in MUM292 extract. This work demonstrates that Streptomyces MUM292 can be a potential antioxidant resource for food and pharmaceutical industries.
  6. Rayanakorn A, Goh BH, Lee LH, Khan TM, Saokaew S
    Sci Rep, 2018 09 06;8(1):13358.
    PMID: 30190575 DOI: 10.1038/s41598-018-31598-w
    Streptococcus suis (S. suis) is a gram-positive bacterial pathogen in pigs which can cause serious infections in human including meningitis, and septicaemia resulting in serious complications. There were discrepancies between different data and little is known concerning associated risk factors of S. suis. A systematic review and meta-analysis was conducted to investigate on S. suis infection risk factors in human. We searched eight relevant databases using the MeSH terms "Streptococcus suis" OR "Streptococcus suis AND infection" limited in human with no time nor language restriction. Out of 4,999 articles identified, 32 and 3 studies were included for systematic review and meta-analysis respectively with a total of 1,454 Streptococcus suis cases reported. S. suis patients were generally adult males and the elderly. The mean age ranged between 37 to 63 years. Meningitis was the most common clinical manifestation, and deafness was the most common sequelae found among survivors followed by vestibular dysfunction. Infective endocarditis was also noted as among the most common clinical presentations associated with high mortality rate in a few studies. Meta-analyses categorized by type of control groups (community control, and non-S. suis sepsis) were done among 850 participants in 3 studies. The combined odd ratios for studies using community control groups and non-S. Suis sepsis as controls respectively were 4.63 (95% CI 2.94-7.29) and 78.00 (95% CI 10.38-585.87) for raw pork consumption, 4.01 (95% CI 2.61-6.15) and 3.03 (95% CI 1.61-5.68) for exposure to pigs or pork, 11.47, (95% CI 5.68-23.14) and 3.07 (95% CI 1.81-5.18) for pig-related occupation and 3.56 (95% CI 2.18-5.80) and 5.84 (95% CI 2.76-12.36) for male sex. The results were found to be significantly associated with S. suis infection and there was non-significant heterogeneity. History of skin injury and underlying diseases were noted only a small percentage in most studies. Setting up an effective screening protocol and public health interventions would be effective to enhance understanding about the disease.
  7. Kemung HM, Tan LT, Khan TM, Chan KG, Pusparajah P, Goh BH, et al.
    Front Microbiol, 2018;9:2221.
    PMID: 30319563 DOI: 10.3389/fmicb.2018.02221
    Methicillin-resistant Staphylococcus aureus (MRSA) pose a significant health threat as they tend to cause severe infections in vulnerable populations and are difficult to treat due to a limited range of effective antibiotics and also their ability to form biofilm. These organisms were once limited to hospital acquired infections but are now widely present in the community and even in animals. Furthermore, these organisms are constantly evolving to develop resistance to more antibiotics. This results in a need for new clinically useful antibiotics and one potential source are the Streptomyces which have already been the source of several anti-MRSA drugs including vancomycin. There remain large numbers of Streptomyces potentially undiscovered in underexplored regions such as mangrove, deserts, marine, and freshwater environments as well as endophytes. Organisms from these regions also face significant challenges to survival which often result in the production of novel bioactive compounds, several of which have already shown promise in drug development. We review the various mechanisms of antibiotic resistance in MRSA and all the known compounds isolated from Streptomyces with anti-MRSA activity with a focus on those from underexplored regions. The isolation of the full array of compounds Streptomyces are potentially capable of producing in the laboratory has proven a challenge, we also review techniques that have been used to overcome this obstacle including genetic cluster analysis. Additionally, we review the in vivo work done thus far with promising compounds of Streptomyces origin as well as the animal models that could be used for this work.
  8. Wong KE, Ngai SC, Chan KG, Lee LH, Goh BH, Chuah LH
    Front Pharmacol, 2019;10:152.
    PMID: 30890933 DOI: 10.3389/fphar.2019.00152
    Colorectal cancer (CRC) is the third most prevalent form of cancer, after lung cancer and breast cancer, with the second highest death incidence. Over the years, natural compounds have been explored as an alternative to conventional cancer therapies such as surgery, radiotherapy, and chemotherapy. Curcumin, an active constituent of turmeric has been associated with various health benefits. It has gained much attention as an anticancer agent due to its ability to regulate multiple cell signaling pathways, including NF-κB, STAT3, activated protein-1 (AP-1), epidermal growth response-1 (Egr-1), and p53, which are crucial in cancer development and progression. Nevertheless, the clinical application of curcumin is greatly restricted because of its low water solubility, poor oral absorption, and rapid metabolism. These issues have led to the development of curcumin nanoformulations to overcome the limitations of the compound. Nanotechnology-based delivery systems have been widely used in improving the delivery of poorly-water soluble drugs. Besides, these systems also come with the added benefits of possible cellular targeting and improvement in cellular uptake. An ideal improved formulation should display a greater anticancer activity compared to free curcumin, and at the same time be non-toxic to the normal cells. In this review, we focus on the design and development of various nanoformulations to deliver curcumin for use in CRC such as liposomes, micelles, polymer nanoparticles, nanogels, cyclodextrin complexes, solid lipid nanoparticles (SLN), phytosomes, and gold nanoparticles. We also discuss the current pre-clinical and clinical evidences of curcumin nanoformulations in CRC therapy, analyse the research gap, and address the future direction of this research area.
  9. Rehman IU, Lai PSM, Lim SK, Lee LH, Khan TM
    BMC Nephrol, 2019 03 25;20(1):102.
    PMID: 30909887 DOI: 10.1186/s12882-019-1294-1
    BACKGROUND: Chronic kidney disease-associated pruritus (CKD-aP) is a well-recognized, frequent and compromising complication among patients on hemodialysis. Despite advancement in basic medical sciences, CKD-aP is still a major complication and a challenge for both physicians and patients to manage. The aim of this study was to estimate the prevalence of CKD-aP among hemodialysis patients in Malaysia, to determine the impact of CKD-aP on sleep quality and any factors associated with CKD-aP.

    METHOD: A multi-centered, cross-sectional study design was conducted from February 2017 to September 2017 at a tertiary hospital and its affiliated dialysis centers, in Kuala Lumpur, Malaysia. Included were patients > 18 years of age who were undergoing hemodialysis and could understand Malay. Participants were asked to fill the Malay 5D-itch scale and the Malay Pittsburgh sleep quality index (PSQI) upon recruitment.

    RESULTS: A total of 334/334 patients were recruited (response rate = 100%). The majority were male (59.6%) and Chinese (61.7%). A total of 61.3% had pruritus, of which most patients (63.4%) reported that their pruritus was mild. More than half (54.1%) reported that they slept > 6 h, and 93.2% experienced no sleep disturbances during the night. However; the overall PSQI median score [IQR] was 6.0 [5.0-9.0]. No significant association was found between demographic and clinical characteristics of patients with the severity of pruritus. Patients with moderate to severe pruritus were found to be 5.47 times more likely to experience poor sleep quality as compared to patients with mild or no pruritus.

    CONCLUSION: In Malaysia, the prevalence of CKD-aP was 61.3%, of which the majority reported that their pruritus was mild. Patients with moderate to severe pruritus were found to be 5.47 times more likely to experience poor sleep quality as compared to patients with mild or no pruritus.

  10. Rehman IU, Lai PS, Kun LS, Lee LH, Chan KG, Khan TM
    Ther Apher Dial, 2020 Feb;24(1):17-25.
    PMID: 31152625 DOI: 10.1111/1744-9987.12862
    CKD-associated pruritus is one of the common symptoms in patients undergoing dialysis, thus contributing to the diminished and compromised quality of life. This study aimed to explore the association between the CKD-associated pruritus on quality of life of patients undergoing hemodialysis in Malaysia. A cross-sectional multicenter study, carried out from February to September 2017 at tertiary care settings in Kuala Lumpur, Malaysia. Patients aged 18 years and above, undergoing hemodialysis, understanding Malay language and willing to participate were included. The CKD-associated pruritus was assessed by using Malay 5D-itch scale and Malay FANLTC questionaiare. To determine the factors associated with pruritus and quality of life, multivariate logistic regression analysis was used having P value < 0.05 as statistically significant. Among n = 334 recruited patients with a response rate of 100%, 59.6% were males and total of 61.3% were having CKD-associated pruritus. The results showed a statistically significant weak negative correlation between CKD-associated pruritus and quality of life. Multivariate linear regression revealed none of these factors were found to be associated with pruritus; however, CKD-associated prurtius was found to be associated with quality of life score. CKD-associated pruritus is have a negative impact on the patient's quality of life including physical, social, mental/emotional, and functional well-being. Despite the high prevalence and negative impact of CKD-associated pruritus on quality of life, it is disregarded by most health care professionals. It is thus pertinent to monitor the potential risk factors and consider providing timely treatment implications for CKD-associated pruritus in hemodialysis patients, in order to improve their quality of life.
  11. Bakrim S, El Omari N, El Hachlafi N, Bakri Y, Lee LH, Bouyahya A
    Foods, 2022 Oct 23;11(21).
    PMID: 36359936 DOI: 10.3390/foods11213323
    Given the stochastic complexity of cancer diseases, the development of chemotherapeutic drugs is almost limited by problems of selectivity and side effects. Furthermore, an increasing number of protective approaches have been recently considered as the main way to limit these pathologies. Natural bioactive compounds, and particularly dietary phenolic compounds, showed major protective and therapeutic effects against different types of human cancers. Indeed, phenolic substances have functional groups that allow them to exert several anti-cancer mechanisms, such as the induction of apoptosis, autophagy, cell cycle arrest at different stages, and the inhibition of telomerase. In addition, in vivo studies show that these phenolic compounds also have anti-angiogenic effects via the inhibition of invasion and angiogenesis. Moreover, clinical studies have already highlighted certain phenolic compounds producing clinical effects alone, or in combination with drugs used in chemotherapy. In the present work, we present a major advance in research concerning the mechanisms of action of the different phenolic compounds that are contained in food medicinal plants, as well as evidence from the clinical trials that focus on them.
  12. Azad SM, Jin Y, Ser HL, Goh BH, Lee LH, Thawai C, et al.
    J Appl Microbiol, 2022 Feb;132(2):772-784.
    PMID: 34260807 DOI: 10.1111/jam.15222
    Extensively produced by members of the genus Streptomyces, piericidins are a large family of microbial metabolites, which consist of main skeleton of 4-pyridinol with methylated polyketide side chain. Nonetheless, these metabolites show differences in their bioactive potentials against micro-organisms, insects and tumour cells. Due to its close structural similarity with coenzyme Q, piericidins also possess an inhibitory activity against NADH dehydrogenase as well as Photosystem II. This review studied the latest research progress of piericidins, covering the chemical structure and physical properties of newly identified members, bioactivities, biosynthetic pathway with gene clusters and future prospect. With the increasing incidence of drug-resistant human pathogen strains and cancers, this review aimed to provide clues for the development of either new potential antibiotics or anti-tumour agents.
  13. Zhang S, Xu J, Lee LH, Chew EP, Wong WP, Chen CH
    IEEE Trans Evol Comput, 2017 Apr;21(2):206-219.
    PMID: 29170617 DOI: 10.1109/TEVC.2016.2592185
    Particle Swarm Optimization (PSO) is a popular metaheuristic for deterministic optimization. Originated in the interpretations of the movement of individuals in a bird flock or fish school, PSO introduces the concept of personal best and global best to simulate the pattern of searching for food by flocking and successfully translate the natural phenomena to the optimization of complex functions. Many real-life applications of PSO cope with stochastic problems. To solve a stochastic problem using PSO, a straightforward approach is to equally allocate computational effort among all particles and obtain the same number of samples of fitness values. This is not an efficient use of computational budget and leaves considerable room for improvement. This paper proposes a seamless integration of the concept of optimal computing budget allocation (OCBA) into PSO to improve the computational efficiency of PSO for stochastic optimization problems. We derive an asymptotically optimal allocation rule to intelligently determine the number of samples for all particles such that the PSO algorithm can efficiently select the personal best and global best when there is stochastic estimation noise in fitness values. We also propose an easy-to-implement sequential procedure. Numerical tests show that our new approach can obtain much better results using the same amount of computational effort.
  14. Duangjai A, Nuengchamnong N, Lee LH, Goh BH, Saokaew S, Suphrom N
    Nat Prod Res, 2019 May;33(10):1491-1494.
    PMID: 29258345 DOI: 10.1080/14786419.2017.1416386
    Azadirachta indica has long been used in traditional medicine. This study focused on isolation and characterisation of active ingredients in the extract, its fractions (NF-EA, NF-AQ, NF-G) and its effect on the cholesterol absorption activity. The NF-EA fraction was identified by marker compounds by LC-ESI-QTOF/MS. Cholesterol absorption activity was performed by measuring the solubility and size of cholesterol micelles. The intestinal motility was also examined by isolated rat's ileum to test the contraction. The extract and its fractions consist of flavonoids and phenolic compounds, like quercetin, kaempferol and myricetin. We found that A. indica extract and NF-EA increase cholesterol micelles size, while the extract, NF-AQ, myricetin and quercetin, reduced the solubility of cholesterol in micelles. The extract and quercetin inhibited the contraction induced by KCl up to 29 and 18%, respectively, and also decreased CaCl2-induced contraction. This finding is in support to traditional uses of A. indica as cholesterol-lowering agents and regulator of gastrointestinal motility.
  15. Bukhsh A, Rehman H, Mallhi TH, Ata H, Rehman IU, Lee LH, et al.
    Hum Vaccin Immunother, 2018 04 03;14(4):952-957.
    PMID: 29333939 DOI: 10.1080/21645515.2017.1415686
    National immunization program of Pakistan does not include Influenza vaccines. The low rate of immunization might be attributed to the poor knowledge of influenza vaccination in Pakistan. Current study was aimed to assess the knowledge and attitude of influenza vaccination among parents. A questionnaire-based cross sectional study was conducted among randomly selected parents with at least one child aged >6 months. The responses were recorded against 27 items questionnaire assessing knowledge, perception, attitude and behaviours of parents. Data were analysed by using appropriate statistical methods. A total 532 responses were recorded with male gender preponderance (65%). Most of the parents (61.1%) reported that their children had received or planned to receive all recommended vaccines in Expanded Program on Immunization (EPI) of Pakistan. Only one third of the parents (24.4%) were aware of the availability of influenza vaccines in Pakistan, and very few (6.6%) reported vaccinating their child against influenza. Exploring the parents' attitudes regarding children vaccination, the top motivator was 'immunization is important to keep my children healthy' (relative index = 0.93, p < 0.000). However, substantial number of parents believed that influenza is not a serious disease (18.5%) and vaccines are accompanied by several side effects (24.6%). A positive attitude was reflected among parents who were aware of influenza vaccines in Pakistan. About 35% participants believed that influenza vaccines are not required for healthy children. Current study demonstrated very low vaccination rate against influenza. Awareness and health literacy regarding influenza vaccine is poor among parents. These findings necessitate the need to appropriately structured awareness programs regarding influenza vaccination among parents.
  16. Lin B, Ser HL, Wang L, Li J, Chan KG, Lee LH, et al.
    Int J Mol Sci, 2023 Feb 28;24(5).
    PMID: 36902078 DOI: 10.3390/ijms24054648
    Matrix metalloproteinase-12 (MMP12), or macrophage metalloelastase, plays important roles in extracellular matrix (ECM) component degradation. Recent reports show MMP12 has been implicated in the pathogenesis of periodontal diseases. To date, this review represents the latest comprehensive overview of MMP12 in various oral diseases, such as periodontitis, temporomandibular joint dysfunction (TMD), orthodontic tooth movement (OTM), and oral squamous cell carcinoma (OSCC). Furthermore, the current knowledge regarding the distribution of MMP12 in different tissues is also illustrated in this review. Studies have implicated the association of MMP12 expression with the pathogenesis of several representative oral diseases, including periodontitis, TMD, OSCC, OTM, and bone remodelling. Although there may be a potential role of MMP12 in oral diseases, the exact pathophysiological role of MMP12 remains to be elucidated. Understanding the cellular and molecular biology of MMP12 is essential, as MMP12 could be a potential target for developing therapeutic strategies targeting inflammatory and immunologically related oral diseases.
  17. Aalilou Y, Moussa H, Lee LH, Bouyahya A, Zengin G, Faouzi MEA
    Fitoterapia, 2024 May 11.
    PMID: 38740345 DOI: 10.1016/j.fitote.2024.106016
    Over the years, the biological activities of seaweeds could have piqued research interest due to their specific functional phytochemistry, which may not be available in terrestrial plants. Seaweeds produce these compounds to overcome and control stressful biotic and abiotic conditions. Additionally, they are potentially excellent sources of highly useful leads in the development of new drugs. Our study aims to unveil, for the first time, an overview of Halopteris scoparia, a species belonging to the Phaeophyceae class and the Stypocaulacea family, by summarizing all available literature data. In this work, we attempt to shed light on its phytochemistry, nutritional values, pharmacological activities, and industrial uses and applications. To gather information related to H. scoparia, relevant keywords were used to search internet databases including Google Scholar, PubMed, ResearchGate, Web of Science, Algae Database, WoRMS database, and DORIS database. The chemical structures were drawn using Chemdraw and verified using the PubChem database. Chemically, this species contains a wide variety of secondary metabolites, such as terpenoids and phenolic compounds. Additionally, other chemical components with nutraceutical value have been identified, such as carbohydrates, proteins, lipids, pigments, minerals and mycosporine like amino acids. Then, holding several reported pharmacological properties, including antioxidant, anti-inflammatory, cytotoxic, dermoprotective, antidepressive, antibacterial, antibiofilm, antifungal, anti-parasitic activities and acute toxicity. In addition to other their applications such as bioconversion and antifouling activities. To confirm the previous pharmacological properties, more comprehensive and systematic in vivo, preclinical, and clinical studies are needed. Furthermore, research is required to uncover the mechanisms of its active compounds and their potential therapeutic effects in treating other diseases such as atherosclerosis, neurodegenerative diseases, and viral infections.
  18. Goh JXH, Tan LT, Goh JK, Chan KG, Pusparajah P, Lee LH, et al.
    Cancers (Basel), 2019 Jun 21;11(6).
    PMID: 31234411 DOI: 10.3390/cancers11060867
    The search for effective methods of cancer treatment and prevention has been a continuous effort since the disease was discovered. Recently, there has been increasing interest in exploring plants and fruits for molecules that may have potential as either adjuvants or as chemopreventive agents against cancer. One of the promising compounds under extensive research is nobiletin (NOB), a polymethoxyflavone (PMF) extracted exclusively from citrus peel. Not only does nobiletin itself exhibit anti-cancer properties, but its derivatives are also promising chemopreventive agents; examples of derivatives with anti-cancer activity include 3'-demethylnobiletin (3'-DMN), 4'-demethylnobiletin (4'-DMN), 3',4'-didemethylnobiletin (3',4'-DMN) and 5-demethylnobiletin (5-DMN). In vitro studies have demonstrated differential efficacies and mechanisms of NOB and its derivatives in inhibiting and killing of colon cancer cells. The chemopreventive potential of NOB has also been well demonstrated in several in vivo colon carcinogenesis animal models. NOB and its derivatives target multiple pathways in cancer progression and inhibit several of the hallmark features of colorectal cancer (CRC) pathophysiology, including arresting the cell cycle, inhibiting cell proliferation, inducing apoptosis, preventing tumour formation, reducing inflammatory effects and limiting angiogenesis. However, these substances have low oral bioavailability that limits their clinical utility, hence there have been numerous efforts exploring better drug delivery strategies for NOB and these are part of this review. We also reviewed data related to patents involving NOB to illustrate the extensiveness of each research area and its direction of commercialisation. Furthermore, this review also provides suggested directions for future research to advance NOB as the next promising candidate in CRC chemoprevention.
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