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A Review on the Effects of Testosterone Supplementation in Hypogonadal Men with Cognitive Impairment

Mohamad NV, Ima-Nirwana S, Chin KY

Curr Drug Targets, 2018;19(8):898-906.
PMID: 28914204 DOI: 10.2174/1389450118666170913162739

Cognitive function and testosterone level of men decline concurrently with age. Low testosterone levels are associated with higher risk of Alzheimer's disease and mild cognitive impairment in men. There are continuous debates on whether this relationship is casual. This paper aims to summarize the current evidence on the association between testosterone level and cognitive function in elderly men. The presence of testosterone, androgen receptor and its responsive genes indicates that testosterone has biological functions in the central nervous system. The ability of the body to convert testosterone into estrogen suggests that part of the actions of testosterone could be mediated by estrogen. Observational studies generally showed that low endogenous testosterone levels were associated with poor cognitive performance in healthy elderly men. Testosterone substitution exerted positive effects on certain cognitive domains in normal and hypogonadal elderly men. In conclusion, testosterone may influence cognitive function in elderly men and its substitution may be considered in men with cognitive impairment and testosterone deficiency.
Targeting Legumain As a Novel Therapeutic Strategy in Cancers

Mai CW, Chung FF, Leong CO

Curr Drug Targets, 2017;18(11):1259-1268.
PMID: 27993111 DOI: 10.2174/1389450117666161216125344

BACKGROUND: Recent reports indicate that the tumor microenvironment plays a pivotal role in cancer development and progression, leading to a paradigm shift in the way cancer is studied and targeted. In contrast to traditional approaches, where only tumor cells are targeted for the treatment, an emerging approach is to develop therapeutics which target the tumor microenvironment while complementing or enhancing current treatments. Legumain (LGMN) is a newly identified target which is highly expressed in the tumor microenvironment and in tumor cells, and holds potential both as a biomarker and as a therapeutic target.
CONCLUSION: This review will be the first to summarize the expression of LGMN in common cancers, as well as its roles in tumorigenesis and metastasis. This review also discusses the current developments and future prospects of targeting LGMN through the development of DNA vaccines, azopeptides, small molecule inhibitors and LGMN activated prodrugs, highlighting the potential of LGMN as a target for cancer therapeutics.
Biological and psychological influences of cross sex hormone in transgender

Ling LS, Sidi H, Lope RAR, Das S, Baharudin A

Curr Drug Targets, 2018 May 11.
PMID: 29749310 DOI: 10.2174/1389450119666180511161420

Transgender is a complex state of bio-psycho-social dimension of human sexuality. It encompasses cognitive-emotional-behavior component that makes the person unique in his or her sexual expression. Transgender tend to use cross sex hormone in order to eradicate their secondary sexual characteristics and to facilitate the shift to their experienced gender. The common masculinising sex hormone use, i.e. Female to Male Treatment Options (FMTO) is testosterone and for feminising hormone i.e. Male to Female Treatment Options (MFTO) is a combination of estrogen with anti-androgen, respectively. Cross sex hormone, i.e. FMTO, or MFTO has biological and psychological influences on the transgender individuals. Nevertheless, cross sex hormone may also poses a range of side effect profiles, varies from the biological to psychosocial impact. The psychological impact can be paramount until it causes severe mental-health problems and even suicide. Numerous ranges of bio-psycho-social influence of cross-sex hormone were highlighted in this review as fundamental core knowledge in the art to know practice when dealing with the treatment options. In psychiatry, the change in the biological appearance may have great influence in the transgender individual, especially in the context of psychosocial and cultural perspective.
MiRNAs Overexpression and Their Role in Breast Cancer: Implications for Cancer Therapeutics

Lee SH, Ng CX, Wong SR, Chong PP

Curr Drug Targets, 2023;24(6):484-508.
PMID: 36999414 DOI: 10.2174/1389450124666230329123409

MicroRNAs have a plethora of roles in various biological processes in the cells and most human cancers have been shown to be associated with dysregulation of the expression of miRNA genes. MiRNA biogenesis involves two alternative pathways, the canonical pathway which requires the successful cooperation of various proteins forming the miRNA-inducing silencing complex (miRISC), and the non-canonical pathway, such as the mirtrons, simtrons, or agotrons pathway, which bypasses and deviates from specific steps in the canonical pathway. Mature miRNAs are secreted from cells and circulated in the body bound to argonaute 2 (AGO2) and miRISC or transported in vesicles. These miRNAs may regulate their downstream target genes via positive or negative regulation through different molecular mechanisms. This review focuses on the role and mechanisms of miRNAs in different stages of breast cancer progression, including breast cancer stem cell formation, breast cancer initiation, invasion, and metastasis as well as angiogenesis. The design, chemical modifications, and therapeutic applications of synthetic anti-sense miRNA oligonucleotides and RNA mimics are also discussed in detail. The strategies for systemic delivery and local targeted delivery of the antisense miRNAs encompass the use of polymeric and liposomal nanoparticles, inorganic nanoparticles, extracellular vesicles, as well as viral vectors and viruslike particles (VLPs). Although several miRNAs have been identified as good candidates for the design of antisense and other synthetic modified oligonucleotides in targeting breast cancer, further efforts are still needed to study the most optimal delivery method in order to drive the research beyond preclinical studies.
Alcohol Addiction- Metabotropic Glutamate Receptor Subtype 5 and its Ligands: How They All Come Together?

Kumar J, Ismail Z, Hatta NH, Baharuddin N, Hapidin H, Get Bee YT, et al.

Curr Drug Targets, 2018;19(8):907-915.
PMID: 28494749 DOI: 10.2174/1389450118666170511144302

In the past decade, many studies have highlighted the role of metabotropic glutamate receptor subtype 5 (mGlu5) modulators in attenuating alcohol-related biological effects such as alcohol consumption, alcohol-seeking and relapse-like behaviors. Taken together, these findings suggest that pharmacological agents acting at mGlu5 could be promising tools in curbing inebriation. mGlu5s are present abundantly in brain regions known to be involved in emotion regulation, motivation and drug administration. On a cellular level, they are primarily located at the postsynaptic part of the neuron where the receptor is functionally linked to various downstream proteins that are involved in cell signaling and gene transcription that mediate the alcohol-induced neuroplasticity. As well, the discovery of a functional link between mGlu5 and a specific isozyme, Protein Kinase C epsilon (PKCε) in mediating the attenuating effects of selective negative allosteric modulators of mGlu5 such as methyl- 6(phenylethynyl)pyridine (MPEP) and 3-((2-methyl-4-thiazolyl)ethynyl)pyridine (MTEP) has sparked interesting speculations. In this article, we shall review the following: the effects of acute and chronic alcohol intake on mGlu5 signaling; the effects of mGlu5 ligands on alcohol-related neurobehavioral changes that are currently being studied both at pre-clinical and clinical stages; and the mechanisms underlying the pharmacological effects of these drugs.
The Potential of Mur Enzymes as Targets for Antimicrobial Drug Discovery

Kumar D, Sarkar N, Roy KK, Bisht D, Kumar D, Mandal B, et al.

Curr Drug Targets, 2023;24(8):627-647.
PMID: 37291783 DOI: 10.2174/1389450124666230608150759

The extensive development in the strains of resistant bacteria is a potential hazard to public health worldwide. This necessitates the development of newer agents with the antibacterial property having new mechanisms of action. Mur enzymes catalyze the steps related to the biosynthesis of peptidoglycan, which constitutes a major part of the cell wall in bacteria. Peptidoglycan increases the stiffness of the cell wall, helping it to survive in unfavorable conditions. Therefore, the inhibition of Mur enzymes may lead to novel antibacterial agents that may help in controlling or overcoming bacterial resistance. Mur enzymes are classified into MurA, MurB, MurC, MurD, MurE, and MurF. Until-date, multiple inhibitors are reported for each class of the Mur enzymes. In this review, we have summarized the development of Mur enzyme inhibitors as antibacterial agents in the last few decades.
The Phosphodiasterase 5-Inhibitors (PDE-5i) for Erectile Dysfunction (ED): A Therapeutic Challenge For Psychiatrists

Koon CS, Sidi H, Kumar J, Xi OW, Das S, Hatta MH, et al.

Curr Drug Targets, 2018;19(12):1366-1377.
PMID: 28215172 DOI: 10.2174/1389450118666170215164747

Erectile function (EF) is a prerequisite for satisfactory sexual intercourse (SI) and central to male sexual functioning. Satisfactory SI eventually initiates orgasm - a biopsychophysiological state of euphoria - leading to a sense of bliss, enjoyment and positive mental well being. For a psychiatrist, treating ED is self-propelled to harmonize these pleasurable experiences alongside with encouragement of physical wellness and sensuality. Hence, the role of PDE-5i is pivotal in this context and constitutes a therapeutic challenge. PDE-5i work via the dopaminergic-oxytocin-nitric oxide pathway by increasing the availability of endothelial's guanosine monophosphate (GMP), immediately causing relaxation of the penile smooth muscle and an erection. The PDE-5i, like sildenafil, vardenafil and tadalafil, are effective in the treatment of ED with some benefits/ flexibilities and disadvantages compared to other treatment modalities. Prescribed PDE-5i exclusively improve EF, fostering male's self-confidence and self-esteem. Treatment failures are associated with factors such as absent (or insufficient) sexual stimulation, psychosexual conflicts and the co-existence of medical disorders. Managing ED requires dealing with underlying medical diseases, addressing other co-morbid sexual dysfunctions like premature ejaculation (PE), and educating the patient on healthy life-styles. Furthermore, by dealing with interpersonal dynamics within the couple and embracing adequate lifestyles (managing stress and revising one's sexual scripts), PDE-5i treatment benefits may be enhanced. In this review, we propose a holistic conceptual framework approach for psychiatric management of patients with ED.
Pharmacological Effects of Turmeric on Learning, Memory and Expression of Muscarinic Receptor Genes (M1, M3 and M5) in Stress-induced Mouse Model

Khalid A, Shakeel R, Justin S, Iqbal G, Shah SAA, Zahid S, et al.

Curr Drug Targets, 2017;18(13):1545-1557.
PMID: 28302036 DOI: 10.2174/1389450118666170315120627

BACKGROUND: Stress is involved in memory impairment through multiple mechanisms, including activation of hypothalamic-pituitary axis, which in turn activates release of corticosterone in blood. Cholinergic system blockade by the muscarinic antagonist, scopolamine, also impairs memory.
OBJECTIVE: This study aimed to investigate the effect of turmeric (20mg/kg) on learning and memory and cholinergic system in a mouse model of stress along with cholinergic blockade.
METHODS: Restrained stress was induced and cholinergic receptors were blocked using scopolamine in mice. Animals were treated with turmeric (turmeric rhizome powder which was also subjected to NMR analyses) and learning and social behavior was examined. Effect of turmeric on cholinergic muscarinic receptors (mAChR; M1, M3 and M5) gene expression was assessed by RT-PCR in both pre-frontal cortex and hippocampus.
RESULTS: Ar-turmerone, curcuminoids and α-linolenic acid were the lead compounds present in turmeric extract. Increased serum corticosterone levels were observed in stressed mice when compared to the control group, while turmeric treatment significantly reduced serum corticosterone level. Turmeric treatment caused an improved learning and memory in Morris water maze test in stressed animals. Social novelty preference was also restored in turmeric treated animals. Following turmeric treatment, M5 expression was improved in the cortex and M3 expression was improved in the hippocampus of stress + scopolamine + turmeric treated group.
CONCLUSIONS: These findings highlight the therapeutic role of turmeric by increasing the expression of M3, M5 and improving learning and memory. Turmeric can be an effective candidate for the treatment of amnesia caused by the stress.
Advances in the Generation of Functional β-cells from Induced Pluripotent Stem Cells As a Cure for Diabetes Mellitus

Kalra K, Chandrabose ST, Ramasamy TS, Kasim NHBA

Curr Drug Targets, 2018;19(13):1463-1477.
PMID: 29874998 DOI: 10.2174/1389450119666180605112917

Diabetes mellitus is one of the leading causes of death worldwide. Loss and functional failure of pancreatic β-cells, the parenchyma cells in the islets of Langerhans, progress diabetes mellitus. The increasing incidence of this metabolic disorder necessitates efficient strategies to produce functional β-cells for treating diabetes mellitus. Human induced Pluripotent Stem Cells (hiPSC), hold potential for treating diabetes ownig to their self-renewal capacity and the ability to differentiate into β- cells. iPSC technology also provides unlimited starting material to generate differentiated cells for regenerative applications. Progress has also been made in establishing in-vitro culture protocols to yield definitive endoderm, pancreatic endoderm progenitor cells and β-cells via different reprogramming strategies and growth factor supplementation. However, these generated β-cells are still immature, lack functional characteristics and exhibit lower capability in reversing the diseases conditions. Current methods employed to generate mature and functional β-cells include; use of small and large molecules to enhance the reprogramming and differentiation efficiency, 3D culture systems to improve the functional properties and heterogeneity of differentiated cells. This review details recent advancements in the generation of mature β-cells by reprogramming stem cells into iPSCs that are further programmed to β-cells. It also provides deeper insight into current reprogramming protocols and their efficacy, focusing on the underlying mechanism of chemical-based approach to generate iPSCs. Furthermore, we have highlighted the recent differentiation strategies both in-vitro and in-vivo to date and the future prospects in the generation of mature β-cells.
The Neurobiology and Psychiatric Perspective of Vaginismus: Linking the Pharmacological and Psycho-Social Interventions

Kadir ZS, Sidi H, Kumar J, Das S, Midin M, Baharuddin N

Curr Drug Targets, 2018;19(8):916-926.
PMID: 28228081 DOI: 10.2174/1389450118666170222153908

Vaginismus is an involuntary muscle contraction of the outer third of vaginal barrel causing sexual penetration almost impossible. It is generally classified under sexual pain disorder (SPD). In Diagnostic and Statistical Manual, 5th edition (DSM-5), it is classified under the new rubric of Genito-Pelvic Pain/Sexual Penetration Disorder. This fear-avoidance condition poses an ongoing significant challenge to the medical and health professionals due to the very demanding needs in health care despite its unpredictable prognosis. The etiology of vaginismus is complex: through multiple biopsycho- social processes, involving bidirectional connections between pelvic-genital (local) and higher mental function (central regulation). It has robust neural and psychological-cognitive loop feedback involvement. The internal neural circuit involves an inter-play of at least two-pathway systems, i.e. both "quick threat assessment" of occipital-limbic-occipital-prefrontal-pelvic-genital; and the chronic pain pathways through the genito-spinothalamic-parietal-pre-frontal system, respectively. In this review, a neurobiology root of vaginismus is deliberated with the central role of an emotional-regulating amygdala, and other neural loop, i.e. hippocampus and neo-cortex in the core psychopathology of fear, disgust, and sexual avoidance. Many therapists view vaginismus as a neglected art-and-science which demands a better and deeper understanding on the clinico-pathological correlation to enhance an effective model for the bio-psycho-social treatment. As vaginismus has a strong presentation in psychopathology, i.e. fear of penetration, phobic avoidance, disgust, and anticipatory anxiety, we highlighted a practical psychiatric approach to the clinical management of vaginismus, based on the current core knowledge in the perspective of neuroscience.
Kratom and Future Treatment for the Opioid Addiction and Chronic Pain: Periculo Beneficium?

Ismail I, Wahab S, Sidi H, Das S, Lin LJ, Razali R

Curr Drug Targets, 2019;20(2):166-172.
PMID: 28443503 DOI: 10.2174/1389450118666170425154120

Kratom (Mitragyna speciosa), a naturally existing plant found in South-East Asia, is traditionally used as a herb to help elevate a person's energy and also to treat numerous medical ailments. Other than the analgesic property, kratom has been used as an agent to overcome opioid withdrawal as it contains natural alkaloids, i.e. mitragynine, 7-hydroxymitragynine, and MGM-9, which has agonist affinity on the opioid receptors, including mu (µ) and kappa (κ). The role of neural reward pathways linked to µ-opioid receptors and both dopaminergic and gamma-Aminobutyric acid (GABA)-ergic interneurons that express µ-opioid receptors were deliberated. However, kratom has been reported to be abused together with other illicit substances with high risk of potential addiction. There are also anecdotes of adverse effects and toxicity of kratom, i.e. tremor, fatigue, seizure, and death. Different countries have distinctive regulation and policy on the plantation and use of this plant when most of the countries banned the use of it because of its addiction problems and side effects. The aim of this review is to highlight on the potential use of kratom, unique 'herbs" as a substitution therapy for chronic pain and opioid addiction, based on the neurobiological perspective of pain and the underlying mechanism of actions of drug addiction.
Experimental fracture protocols in assessments of potential agents for osteoporotic fracture healing using rodent models

Ibrahim N', Mohamad S, Mohamed N, Shuid AN

Curr Drug Targets, 2013 Dec;14(14):1642-50.
PMID: 24350807

Osteoporosis may cause bone fracture even under slight trauma. Osteoporotic fracture has become a major public health problem but until today, the treatments available are not satisfactory. Many pre-clinical testings on animals were done to find new agents that can be sourced from natural products and synthetic drugs for osteoporotic fracture healing. Animal models are more appropriate for fracture healing study than human subject due to several reasons including the ethical issues involved. The bones of rodents are similar to human in term of their morphological change and response to therapy. Small rodents such as rats and mice are suitable animal models for fracture healing studies as they have a similar bone remodeling system to human. To date, there is no specific guideline to carry out fracture healing studies in animal models for the evaluation of new agents. This paper highlights the protocols of various fracture and fixation methods for experimental osteoporotic fracture healing using rodent models.
Update on statins: hope for osteoporotic fracture healing treatment

Ibrahim N', Mohamed N, Shuid AN

Curr Drug Targets, 2013 Dec;14(13):1524-32.
PMID: 23876090

Fracture healing is a process of recovering injured bone tissue forms and functions. Osteoporosis can delay the healing process, which contributes to personal suffering and loss of activities. Osteoporosis patients tend to lose bone mass at the metaphyseal region which require treatment to increase bone mass. Postmenopausal osteoporosis is the most common osteoporosis that occurs in women which subsequently resulted in fractures even under slight trauma. Estrogen Replacement Therapy (ERT), the recommended therapy for postmenopausal osteoporosis, is associated with higher risk of breast cancer, ovarian cancer and cardiovascular diseases. As osteoporotic fractures are becoming a public health issue, alternative treatment is now being thoroughly explored. The potential agent is statins, the HMG-CoA reductase inhibitor which is widely used for hypercholesterolemia treatment. Statins have been found to increase bone mass by stimulation of Bone morphogenetic protein-2 (BMP-2) expression and Vascular Endothelial Growth Factor (VEGF) production. However, these bone forming effects were achieved at very high systemic doses. Therefore, studies on locally applied statins are required to further explore the ability of statins to stimulate bone formation at acceptable doses for better fracture healing. This review highlights the animal and clinical studies on fracture healing promotions by statins and the mechanisms involved.
Recent Advances in Polymer-based Wound Dressings for the Treatment of Diabetic Foot Ulcer: An Overview of State-of-the-art

Hussain Z, Thu HE, Shuid AN, Katas H, Hussain F

Curr Drug Targets, 2018;19(5):527-550.
PMID: 28676002 DOI: 10.2174/1389450118666170704132523

BACKGROUND: Diabetic foot ulcers (DFUs) are the chronic, non-healing complications of diabetic mellitus which compels a significant burden to the patients and the healthcare system. Peripheral vascular disease, diabetic neuropathy, and abnormal cellular and cytokine/chemokine activity are among the prime players which exacerbate the severity and prevent wound repair. Unlike acute wounds, DFUs impose a substantial challenge to the conventional wound dressings and demand the development of novel and advanced wound healing modalities. In general, an ideal wound dressing should provide a moist wound environment, offer protection from secondary infections, eliminate wound exudate and stimulate tissue regeneration.
OBJECTIVE: To date, numerous conventional wound dressings are employed for the management of DFUs but there is a lack of absolute and versatile choice. The current review was therefore aimed to summarize and critically discuss the available evidences related to pharmaceutical and therapeutic viability of polymer-based dressings for the treatment of DFUs.
RESULTS: A versatile range of naturally-originated polymers including chitosan (CS), hyaluronic acid (HA), cellulose, alginate, dextran, collagen, gelatin, elastin, fibrin and silk fibroin have been utilized for the treatment of DFUs. These polymers have been used in the form of hydrogels, films, hydrocolloids, foams, membranes, scaffolds, microparticles, and nanoparticles. Moreover, the wound healing viability and clinical applicability of various mutually modified, semi-synthetic or synthetic polymers have also been critically discussed.
CONCLUSION: In summary, this review enlightens the most recent developments in polymer-based wound dressings with special emphasis on advanced polymeric biomaterials, innovative therapeutic strategies and delivery approaches for the treatment of DFUs.
Plant Polyphenols as Neuroprotective Agents in Parkinson's Disease Targeting Oxidative Stress

Hor SL, Teoh SL, Lim WL

Curr Drug Targets, 2020;21(5):458-476.
PMID: 31625473 DOI: 10.2174/1389450120666191017120505

Parkinson's disease (PD) is the second most prevalent progressive neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the human midbrain. Various ongoing research studies are competing to understand the pathology of PD and elucidate the mechanisms underlying neurodegeneration. Current pharmacological treatments primarily focused on improving dopamine metabolism in PD patients, despite the side effects of long-term usage. In recent years, it is recognized that oxidative stress-mediated pathways lead to neurodegeneration in the brain, which is associated with the pathophysiology of PD. The importance of oxidative stress is often less emphasized when developing potential therapeutic approaches. Natural plant antioxidants have been shown to mediate the oxidative stress-induced effects in PD, which has gained considerable attention in both in vitro and in vivo studies. Yet, clinical trials on natural polyphenol compounds are limited, restricting the potential use of these compounds as an alternative treatment for PD. Therefore, this review provides an understanding of the oxidative stress-induced effects in PD by elucidating the underlying events contributing to oxidative stress and explore the potential use of polyphenols in improving the oxidative status in PD. Preclinical findings have supported the potential of polyphenols in providing neuroprotection against oxidative stress-induced toxicity in PD. However, limiting factors, such as safety and bioavailability of polyphenols, warrant further investigations so as to make them the potential target for clinical applications in the treatment and management of PD.
Cathepsin K inhibitors: a novel target but promising approach in the treatment of osteoporosis

Helali AM, Iti FM, Mohamed IN

Curr Drug Targets, 2013 Dec;14(13):1591-600.
PMID: 23957815

Osteoporosis is a pathologic process characterized by low bone mass with skeletal fragility and an increased risk of fracture. It occurs due to an imbalance between bone resorption and formation. Although current antiresorptive therapy halts bone loss, it does not cure the condition as it also inhibits bone formation. Recent preclinical and clinical trials suggest that the inhibition of resorption by cathepsin K inhibitors increases bone formation. Cathepsin K is a papainlike cysteine protease with high potent collagenase activity and predominantly expressed in osteoclasts. While allowing demineralization, cathepsin K inhibitors suppress the degradation of type I collagen (the major organic matrix of bone) and thus enhancing bone formation. Many of these inhibitors have passed preclinical studies and are presently in clinical trials at different stages of advancement. This review explores the promising role of cathepsin K as a novel antiresorptive for the treatment of osteoporosis.
Phytometabolites Targeting the Warburg Effect in Cancer Cells: A Mechanistic Review

Hasanpourghadi M, Looi CY, Pandurangan AK, Sethi G, Wong WF, Mustafa MR

Curr Drug Targets, 2017;18(9):1086-1094.
PMID: 27033190 DOI: 10.2174/1389450117666160401124842

Phytometabolites are functional elements derived from plants and most of them exhibit therapeutic characteristics such as anti-cancer, anti-inflammatory and anti-oxidant effects. Phytometabolites exert their anti-cancer effect by targeting multiple signaling pathways. One of the remarkable phenomena targeted by phytometabolites is the Warburg effect. The Warburg effect describes the observation that cancer cells exhibit an increased rate of glycolysis and aberrant redox activity compared to normal cells. This phenomenon promotes further cancer development and progression. Recent observations revealed that some phytometabolites could target metabolic-related enzymes (e.g. Hexokinase, Pyruvate kinase M2, HIF-1) in cancer cells, with little or no harm to normal cells. Since hyper-proliferation of cancer cells is fueled by higher cellular metabolism, phytometabolites targeting these metabolic pathways can create synergistic crosstalk with induced apoptotic pathways and sensitize cancer cells to chemotherapeutic agents. In this review, we discuss phytometabolites that target the Warburg effect and the underlying molecular mechanism that leads to tumor growth suppression.
The Effects and Action Mechanisms of Phytoestrogens on Vasomotor Symptoms During Menopausal Transition: Thermoregulatory Mechanism

Hairi HA, Shuid AN, Ibrahim N', Jamal JA, Mohamed N, Mohamed IN

Curr Drug Targets, 2019;20(2):192-200.
PMID: 28814228 DOI: 10.2174/1389450118666170816123740

BACKGROUND: Phytoestrogens have recently been claimed to positively influence menopausal discomforts, including hot flashes. However, little is known about the influence of phytoestrogens on core body temperature during oestrogen fluctuation at menopause.
OBJECTIVE: Previously published findings showed that phytoestrogens could relieve menopausal complaints, thus, the present review was aimed at assessing the effects of phytoestrogens on thermoregulatory mechanism during menopausal transition.
RESULTS: The molecular mechanisms underlying hot flashes are complex. Oestrogen fluctuations cause hypothalamic thermoregulatory centre dysfunction, which leads to hot flashes during menopause. The phytoestrogens of interest, in relation to human health, include isoflavones, lignans, coumestans, and stilbenes, which are widely distributed in nature. The phytoestrogens are capable of reducing hot flashes via their oestrogen-like hormone actions. The potential effects of phytoestrogens on hot flashes and their molecular mechanisms of action on thermoregulatory centre are discussed in this review.
CONCLUSION: The effects of phytoestrogens on these mechanisms may help explain their beneficial effects in alleviating hot flashes and other menopausal discomforts.
New Insight in Improving Therapeutic Efficacy of Antipsychotic Agents: An Overview of Improved In Vitro and In Vivo Performance, Efficacy Upgradation and Future Prospects

Ei Thu H, Hussain Z, Shuid AN

Curr Drug Targets, 2018;19(8):865-876.
PMID: 27894237 DOI: 10.2174/1389450117666161125174625

Psychotic disorders are recognized as severe mental disorders that rigorously affect patient's personality, critical thinking, and perceptional ability. High prevalence, global dissemination and limitations of conventional pharmacological approaches compel a significant burden to the patient, medical professionals and the healthcare system. To date, numerous orally administered therapies are available for the management of depressive disorders, schizophrenia, anxiety, bipolar disorders and autism spectrum problems. However, poor water solubility, erratic oral absorption, extensive first-pass metabolism, low oral bioavailability and short half-lives are the major factors which limit the pharmaceutical significance and therapeutic feasibility of these agents. In recent decades, nanotechnology-based delivery systems have gained remarkable attention of the researchers to mitigate the pharmaceutical issues related to the antipsychotic therapies and to optimize their oral drug delivery, therapeutic outcomes, and patient compliance. Therefore, the present review was aimed to summarize the available in vitro and in vivo evidences signifying the pharmaceutical importance of the advanced delivery systems in improving the aqueous solubility, transmembrane permeability, oral bioavailability and therapeutic outcome of the antipsychotic agents.
Micro-CT assessments of potential anti-osteoporotic agents

Effendy NM, Khamis MF, Shuid AN

Curr Drug Targets, 2013 Dec;14(13):1542-51.
PMID: 24010967

Bone quality assessment is important in assessments of potential agents for the prevention and treatment of osteoporosis. Bone density, microarchitecture and strength are important determinants in osteoporotic study which are widely studied using Dual-Energy X-ray Absorptiometry (DXA), histomorphometry and radiological imaging techniques. In recent years, high resolution micro-CT has become feasible for in vitro or in vivo evaluation of bone architecture. Three-dimensional images of micro-CT reflected high correlations with the conventional histomorphometry and DXA. In comparison to other imaging techniques, micro-CT is the most effective tool in detecting early bone changes for fracture prediction and assessments of potential anti-osteoporotic agents. It is crucial to define an ideal setting with safe radiation doses and appropriate methods for image reconstruction and segmentation to obtain high resolution images. Micro-CT evaluation provides a better insight of bone structure as well as non-metric parameters such as connectivity density, structural model index (SMI) and degree of anisotropy (DA). This non- invasive imaging technique is also equipped with finite element analysis for evaluation of bone biomechanical strength. Micro-CT allows a compressive understanding of the relationships between bone density, microarchitecture and strength which is fundamental to development of pharmacological interventions.

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