Displaying publications 1 - 20 of 54 in total

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  1. Lum PT, Sekar M, Gan SH, Pandy V, Bonam SR
    Saudi J Biol Sci, 2021 Jan;28(1):917-927.
    PMID: 33424383 DOI: 10.1016/j.sjbs.2020.11.037
    Memory impairment (MI) is one of the predominant criteria generally used to identify schizophrenia, dementia and amnesia that are associated with neurodegenerative disorders by evaluating patient's cognitive symptoms. To date, there is no available treatment that can completely mitigate MI. Currently, there is a trend in recent investigations towards symptomatic therapy approaches using a variety of natural compounds. Mangiferin is one of them that have been investigated extensively. Mangiferin is a naturally occurring potent glucoxilxanthone and is mainly isolated from the Mangifera indica (Mango) plant. This review is aimed at providing a comprehensive overview on the efficacy of mangiferin on MI, based on in-vivo animal studies. After screening through articles identified from Scopus and PubMed based on the inclusion and exclusion criteria, a total of 11 articles between 2009 and 2019 were included. The minimum and maximum dose of mangiferin were 10 and 200 mg/kg respectively and administered over the period of 12-154 days. The results of 11 articles showed that mangiferin effectively improved spatial recognition, episodic aversive events, short- and long-term memories primarily occurring via its antioxidant and anti-inflammatory effects. The outcomes of the review revealed that mangiferin improves memory and cognitive impairment in different animal models, indicating that it has potential preventive and therapeutic roles in MI.
  2. Gadhave D, Rasal N, Sonawane R, Sekar M, Kokare C
    Int J Biol Macromol, 2021 Jan 15;167:906-920.
    PMID: 33186648 DOI: 10.1016/j.ijbiomac.2020.11.047
    The research work was intended to formulate teriflunomide (TFM) loaded nano lipid-based (TNLC) carbopol-gellan gum in situ gel (TNLCGHG) and to investigate its therapeutic efficacy against glioma, a brain and spine tumor. Nanoformulation was developed using gellan gum and carbopol 974P as gelling and mucoadhesive agents, respectively, Glyceryl di-behenate and Glyceryl mono-linoleate blend as lipids, and Gelucire 44/14: water blend as surfactant system. Globule size, PDI, zeta potential, encapsulation efficiency, mucoadhesive strength, and nasal permeation were found to be 117.80 nm, 0.56, -21.86 mV, 81.16%, 4.80 g, and 904 μg/cm2, respectively. Anticancer efficacy of TFM-loaded nano lipid-based carbopol-gellan gum in situ gel (TNLCGHG) was determined in human U-87MG glioma cell line. IC50 was found 7.0 μg/mL for TNLCGHG, 4.8 μg/mL for pure TFM, and 78.5 μg/mL for TNLC, which approve the superiority of surfactant along with gellan gum as permeation enhancer. Brain Cmax for technetium (99mTC) labeled intranasal (i.n.) 99mTC-TNLCGHG was found 2-folds higher than 99mTC-TNLC (i.n.) and 99mTC-TNLC intravenous (i.v.) because the TNLCGHG formulation contains surfactant with natural gelling polymers, which promisingly improved drug permeability. Finally, this research revealed encouraging outcomes and successfully developed intranasal TNLCGHG nanoformulation as a novel tool for safe delivery of TFM in glioma patients.
  3. Lum PT, Sekar M, Gan SH, Bonam SR, Shaikh MF
    ACS Chem Neurosci, 2021 Feb 03;12(3):391-418.
    PMID: 33475334 DOI: 10.1021/acschemneuro.0c00824
    Huntington's disease (HD), a neurodegenerative disease, normally starts in the prime of adult life, followed by a gradual occurrence of characteristic psychiatric disturbances and cognitive and motor dysfunction. To the best of our knowledge, there is no treatment available to completely mitigate the progression of HD. Among various therapeutic approaches, exhaustive literature reports have confirmed the medicinal benefits of natural products in HD experimental models. Building on this information, this review presents a brief overview of the neuroprotective mechanism(s) of natural products against in vitro/in vivo models of HD. Relevant studies were identified from several scientific databases, including PubMed, ScienceDirect, Scopus, and Google Scholar. After screening through literature from 2005 to the present, a total of 14 medicinal plant species and 30 naturally isolated compounds investigated against HD based on either in vitro or in vivo models were included in the present review. Behavioral outcomes in the HD in vivo model showed that natural compounds significantly attenuated 3-nitropropionic acid (3-NP) induced memory loss and motor incoordination. The biochemical alteration has been markedly alleviated with reduced lipid peroxidation, increased endogenous enzymatic antioxidants, reduced acetylcholinesterase activity, and increased mitochondrial energy production. Interestingly, following treatment with certain natural products, 3-NP-induced damage in the striatum was ameliorated, as seen histologically. Overall, natural products afforded varying degrees of neuroprotection in preclinical studies of HD via antioxidant and anti-inflammatory properties, preservation of mitochondrial function, inhibition of apoptosis, and induction of autophagy.
  4. Fuloria S, Subramaniyan V, Dahiya R, Dahiya S, Sudhakar K, Kumari U, et al.
    Biology (Basel), 2021 Feb 25;10(3).
    PMID: 33668707 DOI: 10.3390/biology10030172
    Evidence suggests that stem cells exert regenerative potential via the release of extracellular vesicles. Mesenchymal stem cell extracellular vesicles (MSCEVs) offer therapeutic benefits for various pathophysiological ailments by restoring tissues. Facts suggest that MSCEV action can be potentiated by modifying the mesenchymal stem cells culturing methodology and bioengineering EVs. Limited clinical trials of MSCEVs have questioned their superiority, culturing quality, production scale-up and isolation, and administration format. Translation of preclinically successful MSCEVs into a clinical platform requires paying attention to several critical matters, such as the production technique, quantification/characterization, pharmacokinetics/targeting/transfer to the target site, and the safety profile. Keeping these issues as a priority, the present review was designed to highlight the challenges in translating preclinical MSCEV research into clinical platforms and provide evidence for the regenerative potential of MSCEVs in various conditions of the liver, kidney, heart, nervous system, bone, muscle, cartilage, and other organs/tissues.
  5. Malviya R, Tyagi A, Fuloria S, Subramaniyan V, Sathasivam K, Sundram S, et al.
    Polymers (Basel), 2021 May 10;13(9).
    PMID: 34068768 DOI: 10.3390/polym13091531
    Transdermal drug delivery is used to deliver a drug by eliminating the first-pass metabolism, which increases the bioavailability of the drug. The present study aims to formulate the chitosan-tamarind seed polysaccharide composite films and evaluate for the delivery of protein/peptide molecules. Nine formulations were prepared and evaluated by using different parameters, such as physical appearance, folding endurance, thickness of film, surface pH, weight variation, drug content, surface morphology, percentage moisture intake and uptake, drug release kinetics, and drug permeability. The film weight variance was observed between 0.34 ± 0.002 to 0.47 ± 0.003 g. The drug level of the prepared films was found to be between 96 ± 1.21 and 98 ± 1.33μg. Their intake of moisture ranged between 2.83 ± 0.002 and 3.76 ± 0.001 (%). The moisture absorption of the films ranged from 5.33 ± 0.22 to 10.02 ± 0.61 (%). SEM images revealed a smooth film surface, while minor cracks were found in the film after permeation tests. During the first 4 days, drug release was between 13.75 ± 1.64% and 22.54 ± 1.34% and from day 5 to day 6, it was between 72.67 ± 2.13% and 78.33 ± 3.13%. Drug permeation during the first 4 days was 15.78 ± 1.23 %. Drug permeation (%) during the first 4 days was between 15.78 ± 1.23 and 22.49 ± 1.29 and from day 5 to day 6, it was between 71.49 ± 3.21 and 77.93 ± 3.20.
  6. Mat Rani NNI, Mustafa Hussein Z, Mustapa F, Azhari H, Sekar M, Chen XY, et al.
    Eur J Pharm Biopharm, 2021 Aug;165:84-105.
    PMID: 33974973 DOI: 10.1016/j.ejpb.2021.04.021
    Multi antibiotic-resistant bacterial infections are on the rise due to the overuse of antibiotics. Methicillin-resistant Staphylococcus aureus (MRSA) is one of the pathogens listed under the category of serious threats where vancomycin remains the mainstay treatment despite the availability of various antibacterial agents. Recently, decreased susceptibility to vancomycin from clinical isolates of MRSA has been reported and has drawn worldwide attention as it is often difficult to overcome and leads to increased medical costs, mortality, and longer hospital stays. Development of antibiotic delivery systems is often necessary to improve bioavailability and biodistribution, in order to reduce antibiotic resistance and increase the lifespan of antibiotics. Liposome entrapment has been used as a method to allow higher drug dosing apart from reducing toxicity associated with drugs. The surface of the liposomes can also be designed and enhanced with drug-release properties, active targeting, and stealth effects to prevent recognition by the mononuclear phagocyte system, thus enhancing its circulation time. The present review aimed to highlight the possible targeting strategies of liposomes against MRSA bacteremia systemically while investigating the magnitude of this effect on the minimum inhibitory concentration level.
  7. Hamid UZ, Sim MS, Guad RM, Subramaniyan V, Sekar M, Fuloria NK, et al.
    Curr Mol Med, 2021 Aug 06.
    PMID: 34365949 DOI: 10.2174/1566524021666210806162848
    Gastrointestinal (GI) cancers presented an alarmingly high number of new cancer cases worldwide and highly characterised with poor prognosis. The poor overall survival is mainly due to late detection and emerging challenges in treatment, particularly chemoresistance. Thus, the identification of novel molecular targets in GI cancer is highly regarded as the main focus. Recently, long non-coding RNAs (lncRNAs) have been discovered as a potential novel molecular target for combating cancer, as it is highly associated with carcinogenesis and has a great impact on cancer progression. Amongst lncRNAs, HOTIIP has demonstrated a prominent oncogenic regulation in cancer progression, particularly in GI cancers, including oesophageal cancer, gastric cancer, hepatocellular carcinoma, pancreatic cancer and colorectal cancer. This review aimed to present a focused update on the regulatory roles of HOTTIP in GI cancer progression and chemoresistance, as well as deciphering the associated molecular mechanisms underlying their impact on cancer phenotypes and chemoresistance and the key molecules involved. It has been reported that it regulates the expression of various genes and proteins in GI cancers that impacts on the cellular functions, including proliferation, adhesion, migration and invasion, apoptosis, chemosensitivity and tumour differentiation. Furthermore, HOTTIP was also discovered to have a higher diagnostic value as compared to existing diagnostic biomarkers. In overall, HOTTIP has presented itself as a novel therapeutic target and potential diagnostic biomarker in the development of GI cancer treatment.
  8. Malviya R, Sundram S, Fuloria S, Subramaniyan V, Sathasivam KV, Azad AK, et al.
    Polymers (Basel), 2021 Sep 07;13(18).
    PMID: 34577925 DOI: 10.3390/polym13183023
    Polymers from natural sources are widely used as excipients in the formulation of pharmaceutical dosage forms. The objective of this study was to extract and further characterize the tamarind gum polysaccharide (TGP) obtained from Tamarindus indica as an excipient for biomedical applications. Double distilled water was used as a solvent for the extraction of gum while Ethyl alcohol was used as an antisolvent for the precipitation. The results of the Hausner ratio, Carr's index and angle of repose were found to be 0.94, 6.25, and 0.14, respectively, which revealed that the powder is free-flowing with good flowability. The gum was investigated for purity by carrying out chemical tests for different phytochemical constituents and only carbohydrates were found to be present. The swelling index was found to be 87 ± 1%, which shows that TGP has good water intake capacity. The pH of the 1% gum solution was found to be neutral, approximately 6.70 ± 0.01. The ash values such as total ash, sulphated ash, acid insoluble ash, and water-soluble ash were found to be 14.00 ± 1.00%, 13.00 ± 0.05%, 14.04 ± 0.57% and 7.29 ± 0.06%, respectively. The IR spectra confirmed the presence of alcohol, amines, ketones, anhydrides groups. The contact angle was <90°, indicating favorable wetting and good spreading of liquid over the surface The scanning electron micrograph (SEM) revealed that the particle is spherical in shape and irregular. DSC analysis shows a sharp exothermic peak at 350 °C that shows its crystalline nature. The results of the evaluated properties showed that TGP has acceptable properties and can be used as a excipient to formulate dosage forms for biomedical applications.
  9. Sudhakar K, Fuloria S, Subramaniyan V, Sathasivam KV, Azad AK, Swain SS, et al.
    Nanomaterials (Basel), 2021 Sep 29;11(10).
    PMID: 34685005 DOI: 10.3390/nano11102557
    A selected active pharmaceutical ingredient must be incorporated into a cargo carrier in a particular manner so that it achieves its goal. An amalgamation of active pharmaceutical ingredients (APIs) should be conducted in such a manner that it is simple, professional, and more beneficial. Lipids/polymers that are known to be used in nanocarriers for APIs can be transformed into a vesicular formulation, which offers elegant solutions to many problems. Phospholipids with other ingredients, such as ethanol and water, form suitable vesicular carriers for many drugs, overcoming many problems related to poor bioavailability, poor solubility, etc. Ultraflexible liposomes are novel carriers and new frontiers of drug delivery for transdermal systems. Auxiliary advances in vesicular carrier research have been made, enabling polymer-coated ethanolic liposomes to avoid detection by the body's immune system-specifically, the cells of the reticuloendothelial system. Ultraflexible liposomes act as a cargo system and a nanotherapeutic approach for the transport of therapeutic drugs and bioactive agents. Various applications of liposome derivatives in different diseases are emphasized in this review.
  10. Khan TA, Azad AK, Fuloria S, Nawaz A, Subramaniyan V, Akhlaq M, et al.
    Polymers (Basel), 2021 Sep 29;13(19).
    PMID: 34641162 DOI: 10.3390/polym13193345
    The purpose of the present study was to develop emulsions encapsulated by chitosan on the outer surface of a nano droplet containing 5-fluorouracil (5-FU) as a model drug. The emulsions were characterized in terms of size, pH and viscosity and were evaluated for their physicochemical properties such as drug release and skin permeation in vitro. The emulsions containing tween 80 (T80), sodium lauryl sulfate, span 20, and a combination of polyethylene glycol (PEG) and T20 exhibited a release of 88%, 86%, 90% and 92%, respectively. Chitosan-modified emulsions considerably controlled the release of 5-FU compared to a 5-FU solution (p < 0.05). All the formulations enabled transportation of 5-FU through a rat's skin. The combination (T80, PEG) formulation showed a good penetration profile. Different surfactants showed variable degrees of skin drug retention. The ATR-FTIR spectrograms revealed that the emulsions mainly affected the fluidization of lipids and proteins of the stratum corneum (SC) that lead to enhanced drug permeation and retention across the skin. The present study concludes that the emulsions containing a combination of surfactants (Tween) and a co-surfactant (PEG) exhibited the best penetration profile, prevented the premature release of drugs from the nano droplet, enhanced the permeation and the retention of the drug across the skin and had great potential for transdermal drug delivery. Therefore, chitosan-coated 5-FU emulsions represent an excellent possibility to deliver a model drug as a transdermal delivery system.
  11. Sahoo A, Fuloria S, Swain SS, Panda SK, Sekar M, Subramaniyan V, et al.
    Biomedicines, 2021 Oct 20;9(11).
    PMID: 34829734 DOI: 10.3390/biomedicines9111505
    In an emergency, drug repurposing is the best alternative option against newly emerged severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. However, several bioactive natural products have shown potential against SARS-CoV-2 in recent studies. The present study selected sixty-eight broad-spectrum antiviral marine terpenoids and performed molecular docking against two novel SARS-CoV-2 enzymes (main protease or Mpro or 3CLpro) and RNA-dependent RNA polymerase (RdRp). In addition, the present study analysed the physiochemical-toxicity-pharmacokinetic profile, structural activity relationship, and phylogenetic tree with various computational tools to select the 'lead' candidate. The genomic diversity study with multiple sequence analyses and phylogenetic tree confirmed that the newly emerged SARS-CoV-2 strain was up to 96% structurally similar to existing CoV-strains. Furthermore, the anti-SARS-CoV-2 potency based on a protein-ligand docking score (kcal/mol) exposed that the marine terpenoid brevione F (-8.4) and stachyflin (-8.4) exhibited similar activity with the reference antiviral drugs lopinavir (-8.4) and darunavir (-7.5) against the target SARS-CoV-Mpro. Similarly, marine terpenoids such as xiamycin (-9.3), thyrsiferol (-9.2), liouvilloside B (-8.9), liouvilloside A (-8.8), and stachyflin (-8.7) exhibited comparatively higher docking scores than the referral drug remdesivir (-7.4), and favipiravir (-5.7) against the target SARS-CoV-2-RdRp. The above in silico investigations concluded that stachyflin is the most 'lead' candidate with the most potential against SARS-CoV-2. Previously, stachyflin also exhibited potential activity against HSV-1 and CoV-A59 within IC50, 0.16-0.82 µM. Therefore, some additional pharmacological studies are needed to develop 'stachyflin' as a drug against SARS-CoV-2.
  12. Yap KM, Sekar M, Wu YS, Gan SH, Rani NNIM, Seow LJ, et al.
    Saudi J Biol Sci, 2021 Dec;28(12):6730-6747.
    PMID: 34866972 DOI: 10.1016/j.sjbs.2021.07.046
    Breast cancer (BC) has high incidence and mortality rates, making it a major global health issue. BC treatment has been challenging due to the presence of drug resistance and the limited availability of therapeutic options for triple-negative and metastatic BC, thereby urging the exploration of more effective anti-cancer agents. Hesperidin and its aglycone hesperetin, two flavonoids from citrus species, have been extensively evaluated for their anti-cancer potentials. In this review, available literatures on the chemotherapeutic and chemosensitising activities of hesperidin and hesperetin in preclinical BC models are reported. The safety and bioavailability of hesperidin and hesperetin as well as the strategies to enhance their bioavailability are also discussed. Overall, hesperidin and hesperetin can inhibit cell proliferation, migration and BC stem cells as well as induce apoptosis and cell cycle arrest in vitro. They can also inhibit tumour growth, metastasis and neoplastic changes in tissue architecture in vivo. Moreover, the co-administration of hesperidin or hesperetin with doxorubicin, letrozole or tamoxifen can enhance the efficacies of these clinically available agents. These chemotherapeutic and chemosensitising activities of hesperidin and hesperetin have been linked to several mechanisms, including the modulation of signalling pathways, glucose uptake, enzymes, miRNA expression, oxidative status, cell cycle regulatory proteins, tumour suppressor p53, plasma and liver lipid profiles as well as DNA repair mechanisms. However, poor water solubility, extensive phase II metabolism and apical efflux have posed limitations to the bioavailability of hesperidin and hesperetin. Various strategies for bioavailability enhancement have been studied, including the utilisation of nano-based drug delivery systems and the co-administration of hesperetin with other flavonoids. In particular, nanoformulated hesperidin and hesperetin possess greater chemotherapeutic and chemosensitising activities than free compounds. Despite promising preclinical results, further safety and efficacy evaluation of hesperidin and hesperetin as well as their nanoformulations in clinical trials is required to ascertain their potentials to be developed as clinically useful agents for BC treatment.
  13. Azman S, Sekar M, Bonam SR, Gan SH, Wahidin S, Lum PT, et al.
    J Asthma Allergy, 2021;14:641-662.
    PMID: 34163178 DOI: 10.2147/JAA.S296391
    Asthma is a chronic inflammatory disease of the respiratory tract in which the numerous immune cells, including eosinophils, neutrophils, macrophages, T-lymphocytes, mast cells and epithelial lining play key roles. The numerous anti-asthmatic drugs are available in modern medicine to treat asthma, but they have several disadvantages, including side effects and the cost variations, which compromise treatment compliance. The literature review reveals that traditional herbal medicines have good potential as alternative treatment and management for asthma. However, communities hesitated to use the traditional herbal medicines due to lack of established mechanism of action about their anti-asthmatic potential. The present review aimed to summarise the information stated in the literature about the potential effect of traditional medicinal plants (TMPs) conferring protection against ovalbumin (OVA)-induced asthma model. The literature search was conducted in database like PubMed, Scopus, Google Scholar and ScienceDirect. After screening through the literature from 2011 to date, a total of 27 medicinal plants and two polyherbal extracts have been reported to be used as traditional herbal medicines and also utilised to be tested against OVA-induced asthma, were included. We found them to be an important alternative source of treatment for asthma, since some have comparable efficacies with drugs commonly used in the modern system against asthma. All the reported medicinal plants confirmed their traditional use against asthma or its related inflammation. The present review provides faith in traditional information and also offers new insight into the potential of natural products against asthma.
  14. Muhamad Fadzil NS, Sekar M, Gan SH, Bonam SR, Wu YS, Vaijanathappa J, et al.
    Drug Des Devel Ther, 2021;15:2721-2746.
    PMID: 34188450 DOI: 10.2147/DDDT.S299753
    Swertiamarin, a seco-iridoid glycoside, is mainly found in Enicostemma littorale Blume (E. littorale) and exhibits therapeutic activities for various diseases. The present study aimed to provide a review of swertiamarin in terms of its phytochemistry, physicochemical properties, biosynthesis, pharmacology and therapeutic potential. Relevant literature was collected from several scientific databases, including PubMed, ScienceDirect, Scopus and Google Scholar, between 1990 and the present. This review included the distribution of swertiamarin in medicinal plants and its isolation, characterization, physicochemical properties and possible biosynthetic pathways. A comprehensive summary of the pharmacological activities, therapeutic potential and metabolic pathways of swertiamarin was also included after careful screening and tabulation. Based on the reported evidence, swertiamarin meets all five of Lipinski's rules for drug-like properties. Thereafter, the physicochemical properties of swertiamarin were detailed and analyzed. A simple and rapid method for isolating swertiamarin from E. littorale has been described. The present review proposed that swertiamarin may be biosynthesized by the mevalonate or nonmevalonate pathways, followed by the seco-iridoid pathway. It has also been found that swertiamarin is a potent compound with diverse pharmacological activities, including hepatoprotective, analgesic, anti-inflammatory, antiarthritis, antidiabetic, antioxidant, neuroprotective and gastroprotective activities. The anticancer activity of swertiamarin against different cancer cell lines has been recently reported. The underlying mechanisms of all these pharmacological effects are diverse and seem to involve the regulation of different molecular targets, including growth factors, inflammatory cytokines, protein kinases, apoptosis-related proteins, receptors and enzymes. Swertiamarin also modulates the activity of several transcription factors, and their signaling pathways in various pathological conditions are also discussed. Moreover, we have highlighted the toxicity profile, pharmacokinetics and possible structural modifications of swertiamarin. The pharmacological activities and therapeutic potential of swertiamarin have been extensively investigated. However, more advanced studies are required including clinical trials and studies on the bioavailability, permeability and administration of safe doses to offer swertiamarin as a novel candidate for future drug development.
  15. Yap KM, Sekar M, Seow LJ, Gan SH, Bonam SR, Mat Rani NNI, et al.
    PMID: 34548817 DOI: 10.2147/BCTT.S316667
    Globally, breast cancer is the most common cancer type and is one of the most significant causes of deaths in women. To date, multiple clinical interventions have been applied, including surgical resection, radiotherapy, endocrine therapy, targeted therapy and chemotherapy. However, 1) the lack of therapeutic options for metastatic breast cancer, 2) resistance to drug therapy and 3) the lack of more selective therapy for triple-negative breast cancer are some of the major challenges in tackling breast cancer. Given the safe nature of natural products, numerous studies have focused on their anti-cancer potentials. Mangifera indica, commonly known as mango, represents one of the most extensively investigated natural sources. In this review, we provide a comprehensive overview of M. indica extracts (bark, kernel, leaves, peel and pulp) and phytochemicals (mangiferin, norathyriol, gallotannins, gallic acid, pyrogallol, methyl gallate and quercetin) reported for in vitro and in vivo anti-breast cancer activities and their underlying mechanisms based on relevant literature from several scientific databases, including PubMed, Scopus and Google Scholar till date. Overall, the in vitro findings suggest that M. indica extracts and/or phytochemicals inhibit breast cancer cell growth, proliferation, migration and invasion as well as trigger apoptosis and cell cycle arrest. In vivo results demonstrated that there was a reduction in breast tumor xenograft growth. Several potential mechanisms underlying the anti-breast cancer activities have been reported, which include modulation of oxidative status, receptors, signalling pathways, miRNA expression, enzymes and cell cycle regulators. To further explore this medicinal plant against breast cancer, future research directions are addressed. The outcomes of the review revealed that M. indica extracts and their phytochemicals may have potential benefits in the management of breast cancer in women. However, to validate its utility in the creation of innovative and potent therapeutic agents to treat breast cancer, more dedicated research, especially clinical studies are needed to explore the anti-breast cancer potentials of M. indica extracts and their phytochemicals.
  16. Zuraini NZA, Sekar M, Wu YS, Gan SH, Bonam SR, Mat Rani NNI, et al.
    Vasc Health Risk Manag, 2021;17:739-769.
    PMID: 34858028 DOI: 10.2147/VHRM.S328096
    Cardiovascular diseases (CVDs) are one of the leading causes of morbidity and mortality in both developed and developing countries, affecting millions of individuals each year. Despite the fact that successful therapeutic drugs for the management and treatment of CVDs are available on the market, nutritional fruits appear to offer the greatest benefits to the heart and have been proved to alleviate CVDs. Experimental studies have also demonstrated that nutritional fruits have potential protective effects against CVDs. The aim of the review was to provide a comprehensive summary of scientific evidence on the effect of 10 of the most commonly available nutritional fruits reported against CVDs and describe the associated mechanisms of action. Relevant literatures were searched and collected from several scientific databases including PubMed, ScienceDirect, Google Scholar and Scopus. In the context of CVDs, 10 commonly consumed nutritious fruits including apple, avocado, grapes, mango, orange, kiwi, pomegranate, papaya, pineapple, and watermelon were analysed and addressed. The cardioprotective mechanisms of the 10 nutritional fruits were also compiled and highlighted. Overall, the present review found that the nutritious fruits and their constituents have significant benefits for the management and treatment of CVDs such as myocardial infarction, hypertension, peripheral artery disease, coronary artery disease, cardiomyopathies, dyslipidemias, ischemic stroke, aortic aneurysm, atherosclerosis, cardiac hypertrophy and heart failure, diabetic cardiovascular complications, drug-induced cardiotoxicity and cardiomyopathy. Among the 10 nutritional fruits, pomegranate and grapes have been well explored, and the mechanisms of action are well documented against CVDs. All of the nutritional fruits mentioned are edible and readily accessible on the market. Consuming these fruits, which may contain varying amounts of active constituents depending on the food source and season, the development of nutritious fruits-based health supplements would be more realistic for consistent CVD protection.
  17. Yap KM, Sekar M, Fuloria S, Wu YS, Gan SH, Mat Rani NNI, et al.
    Int J Nanomedicine, 2021;16:7891-7941.
    PMID: 34880614 DOI: 10.2147/IJN.S328135
    Despite recent advances in the diagnosis and treatment of breast cancer (BC), it remains a global health issue affecting millions of women annually. Poor prognosis in BC patients is often linked to drug resistance as well as the lack of effective therapeutic options for metastatic and triple-negative BC. In response to these unmet needs, extensive research efforts have been devoted to exploring the anti-BC potentials of natural products owing to their multi-target mechanisms of action and good safety profiles. Various medicinal plant extracts/essential oils and natural bioactive compounds have demonstrated anti-cancer activities in preclinical BC models. Despite the promising preclinical results, however, the clinical translation of natural products has often been hindered by their poor stability, aqueous solubility and bioavailability. There have been attempts to overcome these limitations, particularly via the use of nano-based drug delivery systems (NDDSs). This review highlights the tumour targeting mechanisms of NDDSs, the advantages and disadvantages of the major classes of NDDSs and their current clinical status in BC treatment. Besides, it also discusses the proposed anti-BC mechanisms and nanoformulations of nine medicinal plants' extracts/essential oils and nine natural bioactive compounds; selected via the screening of various scientific databases, including PubMed, Scopus and Google Scholar, based on the following keywords: "Natural Product AND Nanoparticle AND Breast Cancer". Overall, these nanoformulations exhibit improved anti-cancer efficacy against preclinical BC models, with some demonstrating biocompatibility with normal cell lines and mouse models. Further clinical studies are, however, warranted to ascertain their efficacy and biocompatibility in humans.
  18. Azman S, Sekar M, Wahidin S, Gan SH, Vaijanathappa J, Bonam SR, et al.
    J Asthma Allergy, 2021;14:1511-1525.
    PMID: 34938083 DOI: 10.2147/JAA.S298613
    BACKGROUND: Asthma is a chronic lung disease, which causes wheezing, tightness in the chest, shortness of breath and coughing. In the wake of coronavirus disease 2019 (COVID-19), which affect the lungs, asthma patients are at high risk. Embelin, a natural benzoquinone obtained mainly from Embelia ribes Burm, has excellent biological properties, including protection against acute asthma. However, since asthma is a chronic and multi-factorial inflammatory disease, asthma conferred by a single allergen in an animal may not be clinically significant. Therefore, the purpose of the current study was to evaluate the effectiveness of embelin against ovalbumin (OVA)-lipopolysaccharide (LPS)-induced severe airway inflammation in experimental animals and to investigate the plausible mechanism of action.

    METHODS: Rats (n=36) were divided into six groups. Group I served as a normal control. Groups II-VI were sensitised with severe allergens (OVA and LPS) on day 7, 14 and 21, followed by OVA and LPS challenge for 30 min three times/week for 3 weeks. Group II acted as an asthmatic disease control and received only vehicle. On the other hand, groups III-V received embelin (12.5, 25 and 50 mg/kg, P.O. respectively) while group VI received a standard dexamethasone (2.5 mg/kg, P.O.) for 15 days from day 27. Lung function parameters, including the respiratory rate, tidal volume and airflow rate were measured at the end of the experiment (day 42). The total and differential counts of leukocytes in the blood and bronchoalveolar fluid (BALF) were calculated. Th2-mediated serum pro-inflammatory cytokines such as interleukin (IL)-4, IL-5 and IL-13 levels were analyzed. At the end of the study protocol, the lung tissues were removed for a histopathology study. Additionally, a molecular docking simulation on embelin and standard dexamethasone was applied to support the in vivo findings.

    RESULTS: Significant inhibition of eosinophils, neutrophils, lymphocytes and monocytes in the blood and the BALF was seen in the groups, which received embelin (25 and 50 mg/kg) and dexamethasone (2.5 mg/kg). Moreover, the lung function parameters were normalised by embelin (25 and 50 mg/kg) treatment significantly. The lung histopathological changes confirmed the protective effect of embelin against severe airway inflammation. The docking findings indicated good binding efficacy of embelin to IL-13.

    CONCLUSION: Overall, our findings indicate that embelin can alleviate severe airway inflammation in OVA-LPS-induced model of allergic asthma occurring by suppression of Th2-mediated immune response. Due to its promising anti-asthmatic effect, it is recommended that embelin should be investigated in clinical trials against asthma. It should also be further explored against COVID-19 or COVID-like diseases due to its ameliorative effects on cytokines and immune cell infiltration.

  19. Watroly MN, Sekar M, Fuloria S, Gan SH, Jeyabalan S, Wu YS, et al.
    Drug Des Devel Ther, 2021;15:4527-4549.
    PMID: 34764636 DOI: 10.2147/DDDT.S338548
    Anthraquinones (AQs) are found in a variety of consumer products, including foods, nutritional supplements, drugs, and traditional medicines, and have a wide range of pharmacological actions. Rubiadin, a 1,3-dihydroxy-2-methyl anthraquinone, primarily originates from Rubia cordifolia Linn (Rubiaceae). It was first discovered in 1981 and has been reported for many biological activities. However, no review has been reported so far to create awareness about this molecule and its role in future drug discovery. Therefore, the present review aimed to provide comprehensive evidence of Rubiadin's phytochemistry, biosynthesis, physicochemical properties, biological properties and therapeutic potential. Relevant literature was gathered from numerous scientific databases including PubMed, ScienceDirect, Scopus and Google Scholar between 1981 and up-to-date. The distribution of Rubiadin in numerous medicinal plants, as well as its method of isolation, synthesis, characterisation, physiochemical properties and possible biosynthesis pathways, was extensively covered in this review. Following a rigorous screening and tabulating, a thorough description of Rubiadin's biological properties was gathered, which were based on scientific evidences. Rubiadin fits all five of Lipinski's rule for drug-likeness properties. Then, the in depth physiochemical characteristics of Rubiadin were investigated. The simple technique for Rubiadin's isolation from R. cordifolia and the procedure of synthesis was described. Rubiadin is also biosynthesized via the polyketide and chorismate/o-succinylbenzoic acid pathways. Rubiadin is a powerful molecule with anticancer, antiosteoporotic, hepatoprotective, neuroprotective, anti-inflammatory, antidiabetic, antioxidant, antibacterial, antimalarial, antifungal, and antiviral properties. The mechanism of action for the majority of the pharmacological actions reported, however, is unknown. In addition to this review, an in silico molecular docking study was performed against proteins with PDB IDs: 3AOX, 6OLX, 6OSP, and 6SDC to support the anticancer properties of Rubiadin. The toxicity profile, pharmacokinetics and possible structural modifications were also described. Rubiadin was also proven to have the highest binding affinity to the targeted proteins in an in silico study; thus, we believe it may be a potential anticancer molecule. In order to present Rubiadin as a novel candidate for future therapeutic development, advanced studies on preclinical, clinical trials, bioavailability, permeability and administration of safe doses are necessary.
  20. 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.
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