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Impact of pharmacist-delivered interventions on pain-related outcomes: An umbrella review of systematic reviews and meta-analyses

Shrestha S, Iqbal A, Teoh SL, Khanal S, Gan SH, Lee SWH, et al.

Res Social Adm Pharm, 2024 Mar 13.
PMID: 38514293 DOI: 10.1016/j.sapharm.2024.03.005

INTRODUCTION: Pain is a significant healthcare challenge, impacting millions worldwide. Pharmacists have increasingly taken on expanded roles in managing pain, particularly in primary and ambulatory care contexts. This umbrella review aims to systematically evaluate evidence from published systematic reviews that explore the impact of pharmacist-delivered interventions on clinical, humanistic, and economic outcomes related to pain.
METHODS: A systematic search was conducted across six electronic databases, including Ovid Embase, MEDLINE, CINAHL, Scopus, CENTRAL, APA PsycINFO, and DARE, from inception until June 2023. Prior to inclusion, two independent reviewers assessed study titles and abstracts. Following inclusion, an assessment of the methodological quality of the included studies was conducted. AMSTAR 2 was used to evaluate the methodological quality of the included SRs.
RESULTS: From 2055 retrieved titles, 11 systematic reviews were included, with 5 out of 11 being meta-analyses. These SRs encompassed diverse pharmacist-led interventions such as education, medication reviews, and multi-component strategies targeting various facets of pain management. These findings showed favorable clinical outcomes, including reduced pain intensity, improved medication management, enhanced overall physical and mental well-being, and reduced hospitalization durations. Significant pain intensity reductions were found due to pharmacists' interventions, with standardized mean differences (SMDs) ranging from -0.76 to -0.22 across different studies and subgroups. Physical functioning improvements were observed, with SMDs ranging from -0.38 to 1.03. Positive humanistic outcomes were also reported, such as increased healthcare provider confidence, patient satisfaction, and quality of life (QoL). QoL improvements were reported, with SMDs ranging from 0.29 to 1.03. Three systematic reviews examined pharmacist interventions' impact on pain-related economic outcomes, highlighting varying cost implications and the need for robust research methodologies to capture costs and benefits.
CONCLUSION: This umbrella review highlights the effectiveness of pharmacist-delivered interventions in improving clinical, humanistic, and economic outcomes related to pain management. Existing evidence emphasises on the need to integrate pharamacists into multi-disciplinary pain management teams. Further research is needed to investigate innovative care models, such as pharmacist-independent prescribing initiatives within collaborative pain management clinics.
Fulltext Corrigendum: Stylopine: a potential natural metabolite to block vascular endothelial growth factor receptor 2 (VEGFR2) in osteosarcoma therapy

Velayutham NK, Thamaraikani T, Wahab S, Khalid M, Ramachawolran G, Abullais SS, et al.

Front Pharmacol, 2024;15:1343756.
PMID: 38299157 DOI: 10.3389/fphar.2024.1343756

[This corrects the article DOI: 10.3389/fphar.2023.1150270.].
Fulltext Hydroxychloroquine: Key therapeutic advances and emerging nanotechnological landscape for cancer mitigation

Low LE, Kong CK, Yap WH, Siva SP, Gan SH, Siew WS, et al.

Chem Biol Interact, 2023 Dec 01;386:110750.
PMID: 37839513 DOI: 10.1016/j.cbi.2023.110750

Hydroxychloroquine (HCQ) is a unique class of medications that has been widely utilized for the treatment of cancer. HCQ plays a dichotomous role by inhibiting autophagy induced by the tumor microenvironment (TME). Preclinical studies support the use of HCQ for anti-cancer therapy, especially in combination with conventional anti-cancer treatments since they sensitize tumor cells to drugs, potentiating the therapeutic activity. However, clinical evidence has suggested poor outcomes for HCQ due to various obstacles, including non-specific distribution, low aqueous solubility and low bioavailability at target sites, transport across tissue barriers, and retinal toxicity. These issues are addressable via the integration of HCQ with nanotechnology to produce HCQ-conjugated nanomedicines. This review aims to discuss the pharmacodynamic, pharmacokinetic and antitumor properties of HCQ. Furthermore, the antitumor performance of the nanoformulated HCQ is also reviewed thoroughly, aiming to serve as a guide for the HCQ-based enhanced treatment of cancers. The nanoencapsulation or nanoconjugation of HCQ with nanoassemblies appears to be a promising method for reducing the toxicity and improving the antitumor efficacy of HCQ.
Fulltext Current practices, gaps, and opportunities on the role of clinical pharmacists in cancer pain management: Perspectives from Nepal

Shrestha S, Gan SH, Paudyal V, Kc B, Sapkota S

J Oncol Pharm Pract, 2023 Dec;29(8):2049-2056.
PMID: 37847760 DOI: 10.1177/10781552231205025

N/A.
Fulltext Is it possible to generalise superspreading individuals or events of SARS-CoV-2?

Shrestha S, Kaneda Y, Takahashi K, Ozaki A, Gan SH

Lancet Microbe, 2023 Nov;4(11):e858.
PMID: 37640038 DOI: 10.1016/S2666-5247(23)00253-7
Fulltext Factors Contributing to Chronic Kidney Disease following COVID-19 Diagnosis in Pre-Vaccinated Hospitalized Patients

Ramatillah DL, Michael M, Khan K, Natasya N, Sinaga E, Hartuti S, et al.

Vaccines (Basel), 2023 Feb 13;11(2).
PMID: 36851310 DOI: 10.3390/vaccines11020433

In this study, we aim to evaluate the factors that may contribute to the development of chronic kidney disease following COVID-19 infection among hospitalized patients in two private hospitals in Jakarta, Indonesia. This is a retrospective cohort study between March 2020 and September 2021. Patient selection was conducted with a convenience sampling. All patients (n = 378) meeting the inclusion criteria during the study period were enrolled. Various sociodemographic, laboratory test, and diagnostic parameters were measured before the determination of their correlation with the outcome of COVID-19 infection. In this study, all pre-vaccinated patients with COVID-19 had no history of chronic kidney disease (CKD) prior to hospital admission. From this number, approximately 75.7% of the patients developed CKD following COVID-19 diagnosis. Overall, significant correlations were established between the clinical outcome and the CKD status (p = 0.001). Interestingly, there was a significant correlation between serum creatinine level, glomerular filtration rate (GFR), and CKD (p < 0.0001). Oxygen saturation (p = 0.03), admission to the intensive care unit (ICU) (p < 0.0001), and sepsis (p = 0.005) were factors that were significantly correlated with CKD status. Additionally, the type of antibiotic agent used was significantly correlated with CKD (p = 0.011). While 82.1% of patients with CKD survived, the survival rate worsened if the patients had complications from hyperuricemia (p = 0.010). The patients who received levofloxacin and ceftriaxone had the highest (100%) survival rate after approximately 50 days of treatment. The patients who received the antiviral agent combination isoprinosine + oseltamivir + ivermectin fared better (100%) as compared to those who received isoprinosine + favipiravir (8%). Factors, such as hyperuricemia and the antibiotic agent used, contributed to CKD following COVID-19 hospitalization. Interestingly, the patients who received levofloxacin + ceftriaxone and the patients without sepsis fared the best. Overall, patients who develop CKD following COVID-19 hospitalization have a low survival rate.
Discovery of oxindole-based FLT3 inhibitors as a promising therapeutic lead for acute myeloid leukemia carrying the oncogenic ITD mutation

Bender O, Shoman ME, Ali TFS, Dogan R, Celik I, Mollica A, et al.

Arch Pharm (Weinheim), 2023 Feb;356(2):e2200407.
PMID: 36403191 DOI: 10.1002/ardp.202200407

FMS-like tyrosine kinase 3 (FLT3) mutations occur in approximately 30% of acute myeloid leukemia (AML) patients. In the current study, the oxindole chemotype is employed as a structural motif for the design of new FLT3 inhibitors as potential hits for AML irradiation. Cell-based screening was performed with 18 oxindole derivatives and 5a-c inhibited 68%-73% and 83%-91% of internal tandem duplication (ITD)-mutated MV4-11 cell growth for 48- and 72-h treatments while only 0%-2% and 27%-39% in wild-type THP-1 cells. The most potent compound 5a inhibited MV4-11 cells with IC50 of 4.3 µM at 72 h while it was 8.7 µM in THP-1 cells, thus showing two-fold selective inhibition against the oncogenic ITD mutation. The ability of 5a to modulate cell death was examined. High-throughput protein profiling revealed low levels of the growth factors IGFBP-2 and -4 with the blockage of various apoptotic inhibitors such as Survivin. p21 with cellular stress mechanisms was characterized by increased expression of HSP proteins along with TNF-β. Mechanistically, compounds 5a and 5b inhibited FLT3 kinase with IC50 values of 2.49 and 1.45 µM, respectively. Theoretical docking studies supported the compounds' ability to bind to the FLT3 ATP binding site with the formation of highly stable complexes as evidenced by molecular dynamics simulations. The designed compounds also provide suitable drug candidates with no violation of drug likeability rules.
Fulltext SLC1A2 Gene Polymorphism Influences Methamphetamine-Induced Psychosis

Yahya DN, Guad RM, Wu YS, Gan SH, Gopinath SCB, Zakariah HA, et al.

J Pers Med, 2023 Jan 31;13(2).
PMID: 36836504 DOI: 10.3390/jpm13020270

SLC1A2 is a gene encoded for the excitatory amino acid transporter 2 which is responsible for glutamate reuptake from the synaptic cleft in the central nervous system. Recent studies have suggested that polymorphisms on glutamate transporters can affect drug dependence, leading to the development of neurological diseases and psychiatric disorders. Our study investigated the association of rs4755404 single nucleotide polymorphism (SNP) of the SLC1A2 gene with methamphetamine (METH) dependence and METH-induced psychosis and mania in a Malaysian population. The rs4755404 gene polymorphism was genotyped in METH-dependent male subjects (n = 285) and male control subjects (n = 251). The subjects consisted of the four ethnic groups in Malaysia (Malay, Chinese, Kadazan-Dusun, and Bajau). Interestingly, there was a significant association between rs4755404 polymorphism and METH-induced psychosis in the pooled METH-dependent subjects in terms of genotype frequency (p = 0.041). However, there was no significant association between rs4755404 polymorphism and METH dependence. Also, the rs455404 polymorphism was not significantly associated with METH-induced mania for both genotype frequencies and allele frequencies in the METH-dependent subjects, regardless of stratification into the different ethnicities. Our study suggests that the SLC1A2 rs4755404 gene polymorphism confers some susceptibility to METH-induced psychosis, especially for those who carry the GG homozygous genotype.
Fulltext Clinical pharmacists' intervention on pain management in cancer patients (PharmaCAP trial): study protocol for a randomized controlled trial

Shrestha S, Blebil AQ, Teoh SL, Sapkota S, Kc B, Paudyal V, et al.

J Pharm Policy Pract, 2023 Jan 24;16(1):14.
PMID: 36694232 DOI: 10.1186/s40545-022-00505-0

INTRODUCTION: Evidence-based services to support cancer patients with pain via clinical pharmacy services are currently lacking. Therefore, there is a need to undertake a randomized controlled trial (RCT) to explore the effectiveness of clinical pharmacists (CPs)' input into the multidisciplinary team (MDT) in providing better therapeutic outcomes for cancer pain management.
OBJECTIVES: The main aim of this pilot RCT is to determine the feasibility and preliminary efficacy of integrating CPs into the MDT for cancer pain management on the clinical outcomes of cancer patients experiencing pain.
METHODS: This study protocol outlines two-armed multicenter pilot RCT. Cancer patients suffering from pain will be randomly allocated to receive either clinical pharmacy services, i.e., PharmaCAP trial intervention from the CP, or the usual standard care (i.e., control group). Patients will be recruited consecutively from two hospitals in Kathmandu valley, Nepal. The outcomes will be assessed at baseline (pre-intervention) and 4 weeks post-intervention. The primary feasibility outcomes will include eligibility rate, recruitment rate, willingness to participate, acceptability of screening procedures and random allocation, possible contamination between the groups, intervention fidelity and compliance, treatment satisfaction, and patient understanding of the provided interventions. Subsequently, the primary clinical outcome, i.e., pain intensity of cancer patients, will be assessed. The secondary clinical outcomes will include health-related quality of life (HRQoL), anxiety, depression, adverse drug reactions, and patient medication compliance following the integration of CP into the healthcare team.
DISCUSSION: The feasibility and potential for integrating CP involvement in MDT to improve clinical outcomes of cancer patients with pain will be evaluated through the PharmaCAP trial.
TRIAL REGISTRATION: ClinicalTrials.gov NCT05021393. Registered on 25th August 2022.
Fulltext Wound healing properties of a new formulated flavonoid-rich fraction from Dodonaea viscosa Jacq. leaves extract

Subramanian S, Duraipandian C, Alsayari A, Ramachawolran G, Wong LS, Sekar M, et al.

Front Pharmacol, 2023;14:1096905.
PMID: 36817128 DOI: 10.3389/fphar.2023.1096905

Background: Dodonaea viscosa Jacq. (D. viscosa) belongs to the family of Sapindaceae, commonly known as "Sinatha," and is used as a traditional medicine for treating wounds due to its high flavonoids content. However, to date there is no experimental evidence on its flavonoid-rich fraction of D. viscosa formulation as an agent for healing wounds. Objective: The present study aimed to evaluate the wound healing effect of ethyl acetate fraction of D. viscosa leaves on dermal wounds. Methods: The ethyl acetate fraction was produced from a water-ethanol extract of D. viscosa leaves and was quantitatively evaluated using the HPLC technique. The in-vivo wound healing ability of the ethyl acetate fraction of D. viscosa ointment (DVFO, 2.5%w/w and 5%w/w) was investigated in Sprague-Dawley rats utilizing an incision and excision paradigm with povidone-iodine ointment (5% w/w) as a control. The percentage of wound closure, hydroxyproline and hexosamine concentrations, tensile strength and epithelialization duration were measured. Subsequently, histopathology analysis of skin samples as well as western blots were performed for collagen type 3 (COL3A1), basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). Results: The ethyl acetate fraction of D. viscosa revealed flavonoids with high concentrations of quercetin (6.46% w/w) and kaempferol (0.132% w/w). Compared to the control group, the DVFO (2.5% and 5.0% w/w) significantly accelerated wound healing in both models, as demonstrated by quicker wound contraction, epithelialization, elevated hydroxyproline levels and increased tensile strength. Histopathological investigations also revealed that DVFO treatment improved wound healing by re-epithelialization, collagen formation and vascularization of damaged skin samples. Western blot analysis further demonstrated an up-regulation of COL3A, vascular endothelial growth factor and bFGF protein in wound granulation tissue of the DVFO-treated group (p < 0.01). Conclusion: It is concluded that flavonoid-rich D. viscosa ethyl acetate fraction promotes wound healing by up-regulating the expressions of COL3A, VEGF and bFGF protein in wound granulation tissue. However, extensive clinical and pre-clinical research on the flavonoid-rich fraction of D. viscosa is needed to determine its significant impact in the healing of human wounds.
Fulltext Neuroprotective potential of Marsilea quadrifolia Linn against monosodium glutamate-induced excitotoxicity in rats

Subramanian A, Tamilanban T, Sekar M, Begum MY, Atiya A, Ramachawolran G, et al.

Front Pharmacol, 2023;14:1212376.
PMID: 37781695 DOI: 10.3389/fphar.2023.1212376

Background: Excitotoxicity is a condition in which neurons are damaged/injured by the over-activation of glutamate receptors. Excitotoxins play a crucial part in the progression of several neurological diseases. Marsilea quadrifolia Linn (M. quadrifolia) is a very popular aquatic medicinal plant that has been utilised for a variety of therapeutic benefits since ancient times. Its chemical composition is diverse and includes phenolic compounds, tannins, saponins, flavonoids, steroids, terpenoids, alkaloids, carbohydrates and several others that possess antioxidant properties. Objective: The objective of the present study was to investigate the neuroprotective potential of M. quadrifolia against monosodium glutamate (MSG)-induced excitotoxicity in rats. Methods: A high-performance thin-layer chromatography (HPTLC) analysis of chloroform extract of M. quadrifolia (CEMQ) was conducted to identify the major constituents. Further, the in silico docking analysis was carried out on selected ligands. To confirm CEMQ's neuroprotective effects, the locomotor activity, non-spatial memory, and learning were assessed. Results and discussion: The present study confirmed that CMEQ contains quercetin and its derivatives in large. The in-silico findings indicated that quercetin has a better binding affinity (-7.9 kcal/mol) towards the protein target 5EWJ. Animals treated with MSG had 1) a greater reduction in the locomotor score and impairment in memory and learning 2) a greater increase in the blood levels of calcium and sodium and 3) neuronal disorganization, along with cerebral edema and neuronal degeneration in the brain tissues as compared to normal control animals. The changes were however, significantly improved in animals which received standard drug memantine (20 mg/kg) and CEMQ (200 and 400 mg/kg) as compared to the negative control. It is plausible that the changes seen with CEMQ may be attributed to the N-methyl-D-aspartate (NMDA) antagonistic properties. Conclusion: Overall, this study indicated that M. quadrifolia ameliorated MSG-induced neurotoxicity. Future investigations are required to explore the neuroprotective mechanism of M. quadrifolia and its active constituents, which will provide exciting insights in the therapeutic management of neurological disorders.
Fulltext Editorial: The inaugural Monash international health science and technology conference: pharmacology perspectives

Khaw KY, Whittaker MR, Kuruppu S, Chan KG, Gan SH, Goh BH

Front Pharmacol, 2023;14:1208546.
PMID: 37229254 DOI: 10.3389/fphar.2023.1208546
Fulltext Chemistry, Biosynthesis and Pharmacology of Streptonigrin: An Old Molecule with Future Prospects for New Drug Design, Development and Therapy

Nabihah Nasir N, Sekar M, Ravi S, Wong LS, Sisinthy SP, Gan SH, et al.

Drug Des Devel Ther, 2023;17:1065-1078.
PMID: 37064433 DOI: 10.2147/DDDT.S388490

Streptonigrin is an aminoquinone alkaloid isolated from Streptomyces flocculus and is gaining attention as a drug molecule owing to its potential antitumor and antibiotic effects. It was previously used as an anticancer drug but has been discontinued because of its toxic effects. However, according to the most recent studies, the toxicity of streptonigrin and its structurally modified derivatives has been reduced while maintaining their potential pharmacological action at lower concentrations. To date, many investigations have been conducted on this molecule and its derivatives to determine the most effective molecule with low toxicity to enable new drug discovery. Therefore, the main objective of this study is to provide a comprehensive review and to discuss the prospects for streptonigrin and its derived compounds, which may boost the molecule as a highly interesting target molecule for new drug design, development and therapy. To complete this review, relevant literature was collected from several scientific databases, including Google Scholar, PubMed, Scopus and ScienceDirect. Following a complete screening, the obtained information is summarized in the present review to provide a good reference and accelerate the development and utilization of streptonigrin and its derivatives as pharmaceuticals.
Fulltext Celastrol: A Potential Natural Lead Molecule for New Drug Design, Development and Therapy for Memory Impairment

Amir Yusri MA, Sekar M, Wong LS, Gan SH, Ravi S, Subramaniyan V, et al.

Drug Des Devel Ther, 2023;17:1079-1096.
PMID: 37064431 DOI: 10.2147/DDDT.S389977

Celastrol is a naturally occurring chemical isolated from Tripterygium wilfordii Hook. f., root extracts widely known for their neuroprotective properties. In this review, we focus on the efficacy of celastrol in mitigating memory impairment (MI) in both in vivo and in vitro models. Scopus, PubMed and Web of Science databases were utilised to locate pertinent literatures that explore the effects of celastrol in the brain, including its pharmacokinetics, bioavailability, behavioral effects and some of the putative mechanisms of action on memory in many MI models. To date, preclinical studies strongly suggest that celastrol is highly effective in enhancing the cognitive performance of MI animal models, particularly in the memory domain, including spatial, recognition, retention and reference memories, via reduction in oxidative stress and attenuation of neuro-inflammation, among others. This review also emphasised the challenges and potential associated enhancement of medication delivery for MI treatment. Additionally, the potential structural alterations and derivatives of celastrol in enhancing its physicochemical and drug-likeness qualities are examined. The current review demonstrated that celastrol can improve cognitive performance and mitigate MI in several preclinical investigations, highlighting its potential as a natural lead molecule for the design and development of a novel neuroprotective medication.
Fulltext Neuroprotective potency of mangiferin against 3-nitropropionic acid induced Huntington's disease-like symptoms in rats: possible antioxidant and anti-inflammatory mechanisms

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.
Fulltext Stylopine: A potential natural metabolite to block vascular endothelial growth factor receptor 2 (VEGFR2) in osteosarcoma therapy

Velayutham NK, Thamaraikani T, Wahab S, Khalid M, Ramachawolran G, Abullais SS, et al.

Front Pharmacol, 2023;14:1150270.
PMID: 37056983 DOI: 10.3389/fphar.2023.1150270

Vascular endothelial growth factor (VEGF) signals cell survival, cell migration, osteogenesis, cell proliferation, angiogenesis, and vascular permeability by binding to VEGF receptor 2 (VEGFR-2). Osteosarcoma is the most common primary bone cancer, majorly affects young adults. Activation of VEGFR-2 signaling is a therapeutic target for osteosarcoma. The present study aimed to evaluate the potency of stylopine in regulation of the VEGFR-2 signaling pathway and its anti-tumour effect human MG-63 osteosarcoma cells. The in silico study on benzylisoquinoline alkaloids was carried out for analyzing and shortlisting of compounds using a virtual screening, Lipinski's rule, bioavailability graphical RADAR plot, pharmacokinetics, toxicity, and molecular docking studies. Among the benzylisoquinoline alkaloids, stylopine was selected and subjected to in-vitro studies against human MG-63 osteosarcoma cells. Various experiments such as MTT assay, EtBr/AO staining, mitochondrial membrane potential assessment, transwell migration assay, gene expression analysis by a quantitative real time polymerase chain reaction (qRT-PCR) method, SDS-PAGE followed by immunoblotting were performed to evaluate its anti-tumour effect as compared to standard axitinib. The MTT assay indicates that stylopine inhibits cell proliferation in MG-63 cells. Similarly, as confirmed by the EtBr/Ao staining method, the MMP assay indicates that stylopine induces mitochondrial membrane damage and apoptosis as compared to axitinib. Moreover, stylopine inhibits the VEGF-165 induced MG-63 cell migration by a trans-well migration assay. The immunoblotting and qRT-PCR analysis showed that stylopine inhibits the VEGF-165 induced VEGFR2 expression in MG-63 cells. It is concluded that stylopine has potential to regulate VEGFR2 and can inhibit osteosarcoma cells to offer a new drug candidate for the treatment of bone cancer in future.
Fulltext Tilianin: A Potential Natural Lead Molecule for New Drug Design and Development for the Treatment of Cardiovascular Disorders

Khattulanuar FS, Sekar M, Fuloria S, Gan SH, Rani NNIM, Ravi S, et al.

Molecules, 2022 Jan 20;27(3).
PMID: 35163934 DOI: 10.3390/molecules27030673

Cardiovascular disorders (CVDs) are the leading risk factor for death worldwide, and research into the processes and treatment regimens has received a lot of attention. Tilianin is a flavonoid glycoside that can be found in a wide range of medicinal plants and is most commonly obtained from Dracocephalum moldavica. Due to its extensive range of biological actions, it has become a well-known molecule in recent years. In particular, numerous studies have shown that tilianin has cardioprotective properties against CVDs. Hence, this review summarises tilianin's preclinical research in CVDs, as well as its mechanism of action and opportunities in future drug development. The physicochemical and drug-likeness properties, as well as the toxicity profile, were also highlighted. Tilianin can be a natural lead molecule in the therapy of CVDs such as coronary heart disease, angina pectoris, hypertension, and myocardial ischemia, according to scientific evidence. Free radical scavenging, inflammation control, mitochondrial function regulation, and related signalling pathways are all thought to play a role in tilianin's cardioprotective actions. Finally, we discuss tilianin-derived compounds, as well as the limitations and opportunities of using tilianin as a lead molecule in drug development for CVDs. Overall, the scientific evidence presented in this review supports that tilianin and its derivatives could be used as a lead molecule in CVD drug development initiatives.
Fulltext Genistein: A Potential Natural Lead Molecule for New Drug Design and Development for Treating Memory Impairment

Fuloria S, Yusri MAA, Sekar M, Gan SH, Rani NNIM, Lum PT, et al.

Molecules, 2022 Jan 01;27(1).
PMID: 35011497 DOI: 10.3390/molecules27010265

Genistein is a naturally occurring polyphenolic molecule in the isoflavones group which is well known for its neuroprotection. In this review, we summarize the efficacy of genistein in attenuating the effects of memory impairment (MI) in animals. Scopus, PubMed, and Web of Science databases were used to find the relevant articles and discuss the effects of genistein in the brain, including its pharmacokinetics, bioavailability, behavioral effects, and some of the potential mechanisms of action on memory in several animal models. The results of the preclinical studies highly suggested that genistein is highly effective in enhancing the cognitive performance of the MI animal models, specifically in the memory domain, including spatial, recognition, retention, and reference memories, through its ability to reduce oxidative stress and attenuate neuroinflammation. This review also highlighted challenges and opportunities to improve the drug delivery of genistein for treating MI. Along with that, the possible structural modifications and derivatives of genistein to improve its physicochemical and drug-likeness properties are also discussed. The outcomes of the review proved that genistein can enhance the cognitive performance and ameliorate MI in different preclinical studies, thus indicating its potential as a natural lead for the design and development of a novel neuroprotective drug.
Fulltext New challenges in the use of nanomedicine in cancer therapy

Rasool M, Malik A, Waquar S, Arooj M, Zahid S, Asif M, et al.

Bioengineered, 2022 Jan;13(1):759-773.
PMID: 34856849 DOI: 10.1080/21655979.2021.2012907

Nanomedicines are applied as alternative treatments for anticancer agents. For the treatment of cancer, due to the small size in nanometers (nm), specific site targeting can be achieved with the use of nanomedicines, increasing their bioavailability and conferring fewer toxic side effects. Additionally, the use of minute amounts of drugs can lead to cost savings. In addition, nanotechnology is effectively applied in the preparation of such drugs as they are in nm sizes, considered one of the earliest cutoff values for the production of products utilized in nanotechnology. Early concepts described gold nanoshells as one of the successful therapies for cancer and associated diseases where the benefits of nanomedicine include effective active or passive targeting. Common medicines are degraded at a higher rate, whereas the degradation of macromolecules is time-consuming. All of the discussed properties are responsible for executing the physiological behaviors occurring at the following scale, depending on the geometry. Finally, large nanomaterials based on organic, lipid, inorganic, protein, and synthetic polymers have also been utilized to develop novel cancer cures.
Fulltext Baicalein prevents stress-induced anxiety behaviors in zebrafish model

Selvaraj LK, Jeyabalan S, Wong LS, Sekar M, Logeshwari B, Umamaheswari S, et al.

Front Pharmacol, 2022;13:990799.
PMID: 36386131 DOI: 10.3389/fphar.2022.990799

Baicalein is a flavonoid mainly obtained from plants with wide range of biological activities, including neuroprotection. An acute and unexpected chronic stress (UCS) protocol has recently been adapted to zebrafish, a popular vertebrate model in brain research. The present study was aimed to evaluate baicalein's anti-anxiety potential in a zebrafish model by induction, which included neuropharmacological evaluation to determine behavioural parameters in the novel tank diving test (NTDT) and light-dark preference test (LDPT). The toxicity was also assessed using the brine shrimp lethality assay, and the 50% lethal concentration (LC50) was determined. The animals were then stressed for 7 days before being treated with different doses of baicalein (1 and 2 mg/L) for another 7 days in UCS condition. Due to acute stress and UCS, the frequency of entries and time spent in the 1) top region and 2) light area of the novel tank reduced significantly, indicating the existence of elevated anxiety levels. The biological activity of baicalein was demonstrated by its high LC50 values (1,000 μg/ml). Additionally, baicalein administration increased the frequency of entries and duration spent in the light region, indicating a significant decrease in anxiety levels. Overall, the present results showed that baicalein has a therapeutic advantage in reversing the detrimental consequences of UCS and acute stress, making it is a promising lead molecule for new drug design, development, and therapy for stress.

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