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Fulltext Analgesic Activity, Chemical Profiling and Computational Study on Chrysopogon aciculatus

Zihad SMNK, Bhowmick N, Uddin SJ, Sifat N, Rahman MS, Rouf R, et al.

Front Pharmacol, 2018;9:1164.
PMID: 30374304 DOI: 10.3389/fphar.2018.01164

Present study was undertaken to evaluate the analgesic activity of the ethanol extract of Chrysopogon aciculatus. In addition to bioassays in mice, chemical profiling was done by LC-MS and GC-MS to identify phytochemicals, which were further docked on the catalytic site of COX-2 enzymes with a view to suggest the possible role of such phytoconstituents in the observed analgesic activity. Analgesic activity of C. aciculatus was evaluated by acetic acid induced writhing reflex method and hot plate technique. Phytochemical profiling was conducted using liquid chromatography mass spectrometry (LC-MS) and gas chromatography mass spectrometry (GC-MS). In docking studies, homology model of human COX-2 enzyme was prepared using Easy Modeler 4.0 and the identified phytoconstituents were docked using Autodock Vina. Preliminary acute toxicity test of the ethanol extract of C. aciculatus showed no sign of mortality at the highest dose of 4,000 mg/kg. The whole plant extract significantly (p < 0.05) inhibited acetic acid induced writhing in mice at the doses of 500 and 750 mg/kg. The extract delayed the response time in hot plate test in a dose dependent manner. LC-MS analysis of the plant extract revealed the presence of aciculatin, nudaphantin and 5α,8α-epidioxyergosta-6,22-diene-3β-ol. Three compounds namely citronellylisobutyrate; 2,4-dihydroxy-7-methoxy-(2H)-1,4-benzoxazin-3(4H)-one and nudaphantin were identified in the n-hexane fraction by GC-MS. Among these compounds, six were found to be interacting with the binding site for arachidonic acid in COX-2 enzyme. Present study strongly supports the traditional use of C. aciculatus in the management of pain. In conclusion, compounds (tricin, campesterol, gamma oryzanol, and citronellyl isobutyrate) showing promising binding affinity in docking studies, along with previously known anti-inflammatory compound aciculatin can be held responsible for the observed activity.
Fulltext Angelicin-A Furocoumarin Compound With Vast Biological Potential

Mahendra CK, Tan LTH, Lee WL, Yap WH, Pusparajah P, Low LE, et al.

Front Pharmacol, 2020;11:366.
PMID: 32372949 DOI: 10.3389/fphar.2020.00366

Angelicin, a member of the furocoumarin group, is related to psoralen which is well known for its effectiveness in phototherapy. The furocoumarins as a group have been studied since the 1950s but only recently has angelicin begun to come into its own as the subject of several biological studies. Angelicin has demonstrated anti-cancer properties against multiple cell lines, exerting effects via both the intrinsic and extrinsic apoptotic pathways, and also demonstrated an ability to inhibit tubulin polymerization to a higher degree than psoralen. Besides that, angelicin too demonstrated anti-inflammatory activity in inflammatory-related respiratory and neurodegenerative ailments via the activation of NF-κB pathway. Angelicin also showed pro-osteogenesis and pro-chondrogenic effects on osteoblasts and pre-chondrocytes respectively. The elevated expression of pro-osteogenic and chondrogenic markers and activation of TGF-β/BMP, Wnt/β-catenin pathway confirms the positive effect of angelicin bone remodeling. Angelicin also increased the expression of estrogen receptor alpha (ERα) in osteogenesis. Other bioactivities, such as anti-viral and erythroid differentiating properties of angelicin, were also reported by several researchers with the latter even displaying an even greater aptitude as compared to the commonly prescribed drug, hydroxyurea, which is currently on the market. Apart from that, recently, a new application for angelicin against periodontitis had been studied, where reduction of bone loss was indirectly caused by its anti-microbial properties. All in all, angelicin appears to be a promising compound for further studies especially on its mechanism and application in therapies for a multitude of common and debilitating ailments such as sickle cell anaemia, osteoporosis, cancer, and neurodegeneration. Future research on the drug delivery of angelicin in cancer, inflammation and erythroid differentiation models would aid in improving the bioproperties of angelicin and efficacy of delivery to the targeted site. More in-depth studies of angelicin on bone remodeling, the pro-osteogenic effect of angelicin in various bone disease models and the anti-viral implications of angelicin in periodontitis should be researched. Finally, studies on the binding of angelicin toward regulatory genes, transcription factors, and receptors can be done through experimental research supplemented with molecular docking and molecular dynamics simulation.
Fulltext Angiotensin II Type I Receptor Antagonism Attenuates Nicotine-Induced Cardiac Remodeling, Dysfunction, and Aggravation of Myocardial Ischemia-Reperfusion Injury in Rats

Ramalingam A, Budin SB, Mohd Fauzi N, Ritchie RH, Zainalabidin S

Front Pharmacol, 2019;10:1493.
PMID: 31920673 DOI: 10.3389/fphar.2019.01493

Increased exposure to nicotine contributes to the development of cardiac dysfunction by promoting oxidative stress, fibrosis, and inflammation. These deleterious events altogether render cardiac myocytes more susceptible to acute cardiac insults such as ischemia-reperfusion (I/R) injury. This study sought to elucidate the role of angiotensin II type I (AT1) receptors in cardiac injury resulting from prolonged nicotine administration in a rat model. Male Sprague-Dawley rats were given nicotine (0.6 mg/kg ip) for 28 days to induce cardiac dysfunction, alone or in combination with the AT1 receptor antagonist, irbesartan (10 mg/kg, po). Vehicle-treated rats were used as controls. Rat hearts isolated from each experimental group at study endpoint were examined for changes in function, histology, gene expression, and susceptibility against acute I/R injury determined ex vivo. Rats administered nicotine alone exhibited significantly increased cardiac expression of angiotensin II and angiotensin-converting enzyme (ACE) in addition to elevated systolic blood pressure (SBP) and heart rate. Furthermore, nicotine administration markedly reduced left ventricular (LV) performance with concomitant increases in myocardial oxidative stress, fibrosis, and inflammation. Concomitant treatment with irbesartan attenuated these effects, lowering blood pressure, heart rate, oxidative stress, and expression of fibrotic and inflammatory genes. Importantly, the irbesartan-treated group also manifested reduced susceptibility to I/R injury ex vivo. These findings suggest that AT1 receptors play an important role in nicotine-induced cardiac dysfunction, and pharmacological approaches targeting cardiac AT1 receptors may thus benefit patients with sustained exposure to nicotine.
Fulltext Annonaceae: Breaking the Wall of Inflammation

Attiq A, Jalil J, Husain K

Front Pharmacol, 2017;8:752.
PMID: 29104539 DOI: 10.3389/fphar.2017.00752

Inventories of tropical forests have listed Annonaceae as one of the most diverse plant families. For centuries, it is employed in traditional medicines to cure various pathological conditions including snakebite, analgesic, astringent, diarrhea, dysentery, arthritis pain, rheumatism, neuralgia, and weight loss etc. Phytochemical analysis of Annonaceae family have reported the occurrence of alkaloids, flavonoids, triterpenes, diterpenes and diterpene flavone glycosides, sterols, lignans, and annonaceous acetogenin characteristically affiliated with Annonaceae sp. Numerous past studies have underlined the pleotropic pharmacological activities of the crude extracts and isolated compounds from Annonaceae species. This review is an effort to abridge the ethnobotany, morphology, phytochemistry, toxicity, and particularly focusing on the anti-inflammatory activity of the Annonaceae species.
Fulltext Anti-Allergic Properties of Propolis: Evidence From Preclinical and Clinical Studies

Liew KY, Kamise NI, Ong HM, Aw Yong PY, Islam F, Tan JW, et al.

Front Pharmacol, 2021;12:785371.
PMID: 35126124 DOI: 10.3389/fphar.2021.785371

Allergic diseases are a global health burden with increasing prevalence. Side effects of available medications (antihistamines and steroids), lack of patients' perceived effectiveness and high cost of biologic therapies (omalizumab) are challenges to the clinical management of allergic diseases. As allergy symptoms persist for a long time, complementary and alternative medicine (CAM) such as propolis may be considered a potential prophylactic or therapeutic option to avoid long-term medication use. Propolis is a natural resinous substance produced by bees. Although propolis is well known to possess antioxidant, antimicrobial, and anticancer properties, its anti-allergic potential is not fully explored. Several preclinical studies demonstrated the therapeutic effects of propolis extracts against allergic inflammation, asthma, allergic rhinitis, atopic dermatitis, and food allergy, which may be partly attributed to their inhibitory effects on the activation of mast cells and basophils. Clinically, the consumption of propolis as a supplement or an adjunct therapy is safe and attenuates various pathological conditions in asthma. Such an approach may be adopted for atopic dermatitis and allergic rhinitis. Although flavonoids (chrysin, kaempferol, galangin, and pinocembrin) and cinnamic acid derivatives (artepillin C and caffeic acid phenethyl ester) can contribute to the anti-allergic activities, they may not be present in all propolis samples due to variations in the chemical composition. Future studies should relate the anti-allergic activity of propolis with its chemical contents. This mini-review summarizes and discusses existing preclinical and clinical studies reporting the anti-allergic activities of propolis to provide insights into its potential applications in allergic diseases.
Fulltext Anti-Allergic Rhinitis Effects of Medicinal Plants and Their Bioactive Metabolites via Suppression of the Immune System: A Mechanistic Review

Rahim NA, Jantan I, Said MM, Jalil J, Abd Razak AF, Husain K

Front Pharmacol, 2021;12:660083.
PMID: 33927634 DOI: 10.3389/fphar.2021.660083

Allergic rhinitis (AR) is a common inflammatory condition of the nasal mucosa and it is an immunoglobulin E-mediated disease. The incidence and prevalence of AR globally have been escalating over recent years. Antihistamines, intranasal corticosteroids, decongestants, intranasal anticholinergics, intranasal cromolyn, leukotriene receptor antagonists and immunotherapy have been used in the treatment of AR. However, there is a need to search for more effective and safer remedies as many of the current treatments have reported side effects. Medicinal plants have been used traditionally to relief symptoms of AR but their efficacy and safety have not been scientifically proven. In this review, up-to-date reports of studies on the anti-allergic rhinitis of several medicinal plants and their bioactive metabolites through suppression of the immune system are compiled and critically analyzed. The plant samples were reported to suppress the productions of immunoglobulin E, cytokines and eosinophils and inhibit histamine release. The suppression of cytokines production was found to be the main mechanistic effect of the plants to give symptomatic relief. The prospect of these medicinal plants as sources of lead molecules for development of therapeutic agents to treat AR is highlighted. Several bioactive metabolites of the plants including shikonin, okicamelliaside, warifteine, methylwarifteine, luteolin-7-O-rutinoside, tussilagone, petasin, and mangiferin have been identified as potential candidates for development into anti-allergic rhinitis agents. The data collection was mainly from English language articles published in journals, or studies from EBSCOHOST, Medline and Ovid, Scopus, Springer, and Google Scholar databases from the year 1985-2020. The terms or keywords used to find relevant studies were allergic rhinitis OR pollinosis OR hay fever, AND medicinal plant OR single plant OR single herb OR phytotherapy. This comprehensive review serves as a useful resource for medicinal plants with anti-allergic rhinitis potential, understanding the underlying mechanisms of action and for future exploration to find natural product candidates in the development of novel anti-allergic rhinitis agents.
Fulltext Anti-Cancer Properties of the Naturally Occurring Aphrodisiacs: Icariin and Its Derivatives

Tan HL, Chan KG, Pusparajah P, Saokaew S, Duangjai A, Lee LH, et al.

Front Pharmacol, 2016;7:191.
PMID: 27445824 DOI: 10.3389/fphar.2016.00191

Epimedium (family Berberidaceae), commonly known as Horny Goat Weed or Yin Yang Huo, is commonly used as a tonic, aphrodisiac, anti-rheumatic and anti-cancer agent in traditional herbal formulations in Asian countries such as China, Japan, and Korea. The major bioactive compounds present within this plant include icariin, icaritin and icariside II. Although it is best known for its aphrodisiac properties, scientific and pharmacological studies suggest it possesses broad therapeutic capabilities, especially for enhancing reproductive function and osteoprotective, neuroprotective, cardioprotective, anti-inflammatory and immunoprotective effects. In recent years, there has been great interest in scientific investigation of the purported anti-cancer properties of icariin and its derivatives. Data from in vitro and in vivo studies suggests these compounds demonstrate anti-cancer activity against a wide range of cancer cells which occurs through various mechanisms such as apoptosis, cell cycle modulation, anti-angiogenesis, anti-metastasis and immunomodulation. Of note, they are efficient at targeting cancer stem cells and drug-resistant cancer cells. These are highly desirable properties to be emulated in the development of novel anti-cancer drugs in combatting the emergence of drug resistance and overcoming the limited efficacy of current standard treatment. This review aims to summarize the anti-cancer mechanisms of icariin and its derivatives with reference to the published literature. The currently utilized applications of icariin and its derivatives in cancer treatment are explored with reference to existing patents. Based on the data compiled, icariin and its derivatives are shown to be compounds with tremendous potential for the development of new anti-cancer drugs.
Fulltext Anti-High Mobility Group Box-1 Monoclonal Antibody Attenuates Seizure-Induced Cognitive Decline by Suppressing Neuroinflammation in an Adult Zebrafish Model

Paudel YN, Othman I, Shaikh MF

Front Pharmacol, 2020;11:613009.
PMID: 33732146 DOI: 10.3389/fphar.2020.613009

Epilepsy is a chronic brain disease afflicting around 70 million global population and is characterized by persisting predisposition to generate epileptic seizures. The precise understanding of the etiopathology of seizure generation is still elusive, however, brain inflammation is considered as a major contributor to epileptogenesis. HMGB1 protein being an initiator and crucial contributor of inflammation is known to contribute significantly to seizure generation via activating its principal receptors namely RAGE and TLR4 reflecting a potential therapeutic target. Herein, we evaluated an anti-seizure and memory ameliorating potential of an anti-HMGB1 monoclonal antibody (mAb) (1, 2.5 and 5 mg/kg, I.P.) in a second hit Pentylenetetrazol (PTZ) (80 mg/kg, I.P.) induced seizure model earlier stimulated with Pilocarpine (400 mg/kg, I.P.) in adult zebrafish. Pre-treatment with anti-HMGB1 mAb dose-dependently lowered the second hit PTZ-induced seizure but does not alter the disease progression. Moreover, anti-HMGB1 mAb also attenuated the second hit Pentylenetetrazol induced memory impairment in adult zebrafish as evidenced by an increased inflection ration at 3 and 24 h trail in T-maze test. Besides, decreased level of GABA and an upregulated Glutamate level was observed in the second hit PTZ induced group, which was modulated by pre-treatment with anti-HMGB1 mAb. Inflammatory responses occurred during the progression of seizures as evidenced by upregulated mRNA expression of HMGB1, TLR4, NF-κB, and TNF-α, in a second hit PTZ group, which was in-turn downregulated upon pre-treatment with anti-HMGB1 mAb reflecting its anti-inflammatory potential. Anti-HMGB1 mAb modulates second hit PTZ induced changes in mRNA expression of CREB-1 and NPY. Our findings indicates anti-HMGB1 mAb attenuates second hit PTZ-induced seizures, ameliorates related memory impairment, and downregulates the seizure induced upregulation of inflammatory markers to possibly protect the zebrafish from the incidence of further seizures through via modulation of neuroinflammatory pathway.
Fulltext Anti-Inflammatory Effects of Thymoquinone in Atherosclerosis: A Mini Review

Leong XF, Choy KW, Alias A

Front Pharmacol, 2021;12:758929.
PMID: 34975474 DOI: 10.3389/fphar.2021.758929

Atherosclerosis poses serious health problems and increases the risk of various cardiovascular diseases, including myocardial infarction, heart failure, ischemic stroke, and peripheral arterial disease. Atherosclerosis patients require long-term medications to prevent complications, some of which are costly and may result in unwanted adverse reactions. Natural products have emerged as potential sources of bioactive compounds that provide health benefits in cardiovascular diseases. Increased inflammation and vascular remodeling have been associated with atherosclerosis pathogenesis. The molecules involved in signaling pathways are considered valuable targets for new treatment approaches. Therefore, this review aimed to summarize the available evidence of the anti-inflammatory effects of thymoquinone, the major active compound isolated from Nigella sativa L., via inflammatory signaling pathways in atherosclerosis. Specifically, nuclear factor-κB and mitogen-activated protein kinase signaling pathways were considered. Furthermore, the potential toxic effects elicited by thymoquinone were addressed. These findings suggest a potential role of thymoquinone in managing atherosclerosis, and further studies are required to ascertain its effectiveness and safety profile.
Fulltext Anti-cancer properties of boswellic acids: mechanism of action as anti-cancerous agent

Trivedi VL, Soni R, Dhyani P, Sati P, Tejada S, Sureda A, et al.

Front Pharmacol, 2023;14:1187181.
PMID: 37601048 DOI: 10.3389/fphar.2023.1187181

With the advent of highly effective plant-based medications with few or no side effects, the use of phytomedicines against complex diseases such as cancer is becoming more widespread. The broadly recognized pentacyclic triterpenes known as boswellic acids (BAs) are derived from the oleogum resin, or frankincense, extracted from the plant species of the genus Boswellia. The frankincense mixture contains various BA types, each having a different potential and helping treat certain cancers. This review focuses on details regarding the traits of the BAs, their roles as anti-cancer agents, the mechanism underlying their activities, and the function of their semi-synthetic derivatives in managing and treating certain cancers. The review also explores the biological sources of BAs, how they are conserved, and how biotechnology might help preserve and improve in vitro BA production. The review concludes that the BAs and their semi-synthetic derivatives are effective against a broad spectrum of cancer cell lines. The detailed information in the review can be helpful for researchers to gain more information about BAs and BA-based medications for efficient and cost-effective cancer treatments.
Fulltext Anti-gout potential of Malaysian medicinal plants

Abu Bakar FI, Abu Bakar MF, Rahmat A, Abdullah N, Sabran SF, Endrini S

Front Pharmacol, 2018;9:261.
PMID: 29628890 DOI: 10.3389/fphar.2018.00261

Gout is a type of arthritis that causes painful inflammation in one or more joints. In gout, elevation of uric acid in the blood triggers the formation of crystals, causing joint pain. Malaysia is a mega-biodiversity country that is rich in medicinal plants species. Therefore, its flora might offer promising therapies for gout. This article aims to systematically review the anti-gout potential of Malaysian medicinal plants. Articles on gout published from 2000 to 2017 were identified using PubMed, Scopus, ScienceDirect, and Google Scholar with the following keyword search terms: "gout," "medicinal plants," "Malaysia," "epidemiology," "in vitro," and "in vivo." In this study, 85 plants were identified as possessing anti-gout activity. These plants had higher percentages of xanthine oxidase inhibitory activity (>85%); specifically, the Momordica charantia, Chrysanthemum indicum, Cinnamomum cassia, Kaempferia galanga, Artemisia vulgaris, and Morinda elliptica had the highest values, due to their diverse natural bioactive compounds, which include flavonoids, phenolics, tannin, coumarins, luteolin, and apigenin. This review summarizes the anti-gout potential of Malaysian medicinal plants but the mechanisms, active compounds, pharmacokinetics, bioavailability, and safety of the plants still remain to be elucidated.
Fulltext Anti-neuroinflammatory Activity of Elephantopus scaber L. via Activation of Nrf2/HO-1 Signaling and Inhibition of p38 MAPK Pathway in LPS-Induced Microglia BV-2 Cells

Chan CK, Tan LT, Andy SN, Kamarudin MNA, Goh BH, Kadir HA

Front Pharmacol, 2017;8:397.
PMID: 28680404 DOI: 10.3389/fphar.2017.00397

Elephantopus scaber L. (family: Asteraceae) has been traditionally utilized as a folkloric medicine and scientifically shown to exhibit anti-inflammatory activities in various in vivo inflammatory models. Given the lack of study on the effect of E. scaber in neuroinflammation, this study aimed to investigate the anti-neuroinflammatory effect and the underlying mechanisms of ethyl acetate fraction from the leaves of E. scaber (ESEAF) on the release of pro-inflammatory mediators in lipopolysaccharide (LPS)-induced microglia cells (BV-2). Present findings showed that ESEAF markedly attenuated the translocation of NF-κB to nucleus concomitantly with the significant mitigation on the LPS-induced production of NO, iNOS, COX-2, PGE2, IL-1β, and TNF-α. These inflammatory responses were reduced via the inhibition of p38. Besides, ESEAF was shown to possess antioxidant activities evident by the DPPH and SOD scavenging activities. The intracellular catalase enzyme activity was enhanced by ESEAF in the LPS-stimulated BV-2 cells. Furthermore, the formation of ROS induced by LPS in BV-2 cells was reduced upon the exposure to ESEAF. Intriguingly, the reduction of ROS was found in concerted with the activation of Nrf2 and HO-1. It is conceivable that the activation promotes the scavenging power of antioxidant enzymes as well as to ameliorate the inflammatory response in LPS-stimulated BV-2 cells. Finally, the safety profile analysis through oral administration of ESEAF at 2000 mg/kg did not result in any mortalities, adverse effects nor histopathologic abnormalities of organs in mice. Taken altogether, the cumulative findings suggested that ESEAF holds the potential to develop as nutraceutical for the intervention of neuroinflammatory disorders.
Fulltext Anticancer Activities of Surfactin and Potential Application of Nanotechnology Assisted Surfactin Delivery

Wu YS, Ngai SC, Goh BH, Chan KG, Lee LH, Chuah LH

Front Pharmacol, 2017;8:761.
PMID: 29123482 DOI: 10.3389/fphar.2017.00761

Surfactin, a cyclic lipopeptide biosurfactant produced by various strains of Bacillus genus, has been shown to induce cytotoxicity against many cancer types, such as Ehrlich ascites, breast and colon cancers, leukemia and hepatoma. Surfactin treatment can inhibit cancer progression by growth inhibition, cell cycle arrest, apoptosis, and metastasis arrest. Owing to the potent effect of surfactin on cancer cells, numerous studies have recently investigated the mechanisms that underlie its anticancer activity. The amphiphilic nature of surfactin allows its easy incorporation nano-formulations, such as polymeric nanoparticles, micelles, microemulsions, liposomes, to name a few. The use of nano-formulations offers the advantage of optimizing surfactin delivery for an improved anticancer therapy. This review focuses on the current knowledge of surfactin properties and biosynthesis; anticancer activity against different cancer models and the underlying mechanisms involved; as well as the potential application of nano-formulations for optimal surfactin delivery.
Fulltext Antioxidant and Anti-Inflammatory Effects of Genus Gynura: A Systematic Review

Tan JN, Mohd Saffian S, Buang F, Jubri Z, Jantan I, Husain K, et al.

Front Pharmacol, 2020;11:504624.
PMID: 33328981 DOI: 10.3389/fphar.2020.504624

Background:Gynura species have been used traditionally to treat various ailments, such as fever, pain, and to control blood glucose level. This systematic review critically discusses studies regarding Gynura species that exhibited antioxidant and anti-inflammatory effects, thus providing perspectives and instructions for future research of the plants as a potential source of new dietary supplements or medicinal agents. Methods: A literature search from internet databases of PubMed, Scopus, Science Direct, e-theses Online Service, and ProQuest was carried out using a combination of keywords such as "Gynura," "antioxidant," "anti-inflammatory," or other related words. Research articles were included in this study if they were experimental (in vitro and in vivo) or clinical studies on the antioxidant or anti-inflammatory effects of Gynura species and if they were articles published in English. Results: Altogether, 27 studies on antioxidant and anti-inflammatory effects of Gynura species were selected. The antioxidant effects of Gynura species were manifested by inhibition of reactive oxygen species production and lipid peroxidation, modulation of glutathione-related parameters, and enzymatic antioxidant production or activities. The anti-inflammatory effects of Gynura species were through the modulation of inflammatory cytokine production, inhibition of prostaglandin E2 and nitric oxide production, cellular inflammatory-related parameters, and inflammation in animal models. The potential anti-inflammatory signaling pathways modulated by Gynura species are glycogen synthase kinase-3, nuclear factor erythroid 2-related factor 2, PPARγ, MAPK, NF-κB, and PI3K/Akt. However, most reports on antioxidant and anti-inflammatory effects of the plants were on crude extracts, and the chemical constituents contributing to bioactivities were not clearly understood. There is a variation in quality of studies in terms of design, conduct, and interpretation, and in-depth studies on the underlying mechanisms involved in antioxidant and anti-inflammatory effects of the plants are in demand. Moreover, there is limited clinical study on antioxidant and anti-inflammatory effects of Gynura species. Conclusion: This review highlighted antioxidant and anti-inflammatory effects of genus Gynura and supported their traditional uses to treat oxidative stress and inflammatory-related diseases. This review is expected to catalyze further studies on genus Gynura. However, extensive preclinical data need to be generated from toxicity and pharmacokinetic studies before clinical studies can be pursued for their development into clinical medicines to treat oxidative stress and inflammatory conditions.
Fulltext Antioxidant and Oxidative Stress: A Mutual Interplay in Age-Related Diseases

Tan BL, Norhaizan ME, Liew WP, Sulaiman Rahman H

Front Pharmacol, 2018;9:1162.
PMID: 30405405 DOI: 10.3389/fphar.2018.01162

Aging is the progressive loss of organ and tissue function over time. Growing older is positively linked to cognitive and biological degeneration such as physical frailty, psychological impairment, and cognitive decline. Oxidative stress is considered as an imbalance between pro- and antioxidant species, which results in molecular and cellular damage. Oxidative stress plays a crucial role in the development of age-related diseases. Emerging research evidence has suggested that antioxidant can control the autoxidation by interrupting the propagation of free radicals or by inhibiting the formation of free radicals and subsequently reduce oxidative stress, improve immune function, and increase healthy longevity. Indeed, oxidation damage is highly dependent on the inherited or acquired defects in enzymes involved in the redox-mediated signaling pathways. Therefore, the role of molecules with antioxidant activity that promote healthy aging and counteract oxidative stress is worth to discuss further. Of particular interest in this article, we highlighted the molecular mechanisms of antioxidants involved in the prevention of age-related diseases. Taken together, a better understanding of the role of antioxidants involved in redox modulation of inflammation would provide a useful approach for potential interventions, and subsequently promoting healthy longevity.
Fulltext Antithrombotic Regimens in Patients With Percutaneous Coronary Intervention Whom an Anticoagulant Is Indicated: A Systematic Review and Network Meta-Analysis

Bunmark W, Jinatongthai P, Vathesatogkit P, Thakkinstian A, Reid CM, Wongcharoen W, et al.

Front Pharmacol, 2018;9:1322.
PMID: 30510510 DOI: 10.3389/fphar.2018.01322

Background: Patients undergoing percutaneous coronary intervention (PCI) who require anticoagulant therapy are at increased risk of bleeding. The optimal regimen for these patients is uncertain. This study aimed to compare safety and efficacy of antithrombotic regimens used in patients undergoing PCI with concomitant anticoagulant therapy. Methods: A systematic review and network meta-analysis was performed among studies comparing antithrombotic regimens for anticoagulated patients undergoing PCI. The primary outcome of interest was major bleeding. The secondary outcomes were coronary events. The reference intervention was classic triple therapy (aspirin plus clopidogrel plus VKA). Cluster rank incorporating risk (major bleeding) and benefit (all-cause death) was performed to identify the most appropriate regimen(s). Results: There were 3 RCTs (6 interventions) and 29 non-RCTs (8 interventions) that met the inclusion criteria with 22,179 patients. Network meta-analysis of RCTs indicated that dual therapy (DT), either with vitamin K antagonist (VKA) or direct anticoagulant (DOAC) plus an antiplatelet, significantly reduced the risk of major bleeding compared to triple therapy (TT) [pooled RR of 0.51 (0.30-0.87) and 0.68 (0.49-0.94), respectively]. In addition, VKA-DT significantly reduced the risk of all-cause death compared to TT [pooled RR of 0.40 (0.17-0.93)]. Results from network meta-analysis of non-RCT paralleled that of RCTs. No significant differences of coronary events were found. Conclusions: In conclusion, for anticoagulated patients undergoing PCI, dual therapy, either with warfarin or DOAC plus an antiplatelet, should be considered due to its optimal balance on efficacy and safety.
Assessment of Cardiovascular Functioning Among Regular Kratom (Mitragyna speciosa Korth) Users: A Case Series

Leong Bin Abdullah MFI, Singh D

Front Pharmacol, 2021;12:723567.
PMID: 34504428 DOI: 10.3389/fphar.2021.723567

Multiorgan toxicities have been extensively reported in kratom (Mitragyna speciosa Korth) users in Western countries but not in Southeast Asia. Existing literature argued that this discrepancy may be due to underreporting of kratom-related toxicity cases in Southeast Asia. Hence, this case series filled the research gap by clinically assessing the cardiovascular functioning and serum mitragynine level of regular kratom users in its traditional settings in Malaysia. Nine regular kratom users without history of polysubstance use were recruited from the same community via snowball sampling and were subjected to electrocardiogram (ECG) and echocardiogram assessments. Serum mitragynine analysis was also performed by solid-phase extraction and liquid chromatography-tandem mass spectrometry. The mean serum mitragynine level was 10.3 mg/L (SD = 6.9) and ranged from 2.5 mg/L to 22.4 mg/L. Those who consumed an average daily quantity of four or more glasses of brewed kratom juice (p = 0.045) and those who had prolonged QTc intervals (p = 0.017) had significantly higher serum mitragynine level. Echocardiographic findings of all the respondents were normal except one reported left ventricular hypertrophy and another had trivial tricuspid regurgitation with pulmonary artery systolic pressure (PASP) of 10 + 5 mmHg. Regular kratom use without concomitant use of other illicit substances may not provoke any risk of cardiovascular impairment or toxicity except for prolonged QTc interval, which appeared to be dose dependent. However, as this study was limited by a small sample size, future studies with larger sample size are warranted to confirm our findings.
Fulltext Assessment of Medication Adherence in Saudi Patients With Type II Diabetes Mellitus in Khobar City, Saudi Arabia

AlQarni K, AlQarni EA, Naqvi AA, AlShayban DM, Ghori SA, Haseeb A, et al.

Front Pharmacol, 2019;10:1306.
PMID: 31787894 DOI: 10.3389/fphar.2019.01306

Objective: Medication adherence is defined as taking medications as advised and prescribed by health care professionals for stated duration. Diabetes mellitus (DM) is one of the most common chronic illnesses in Saudi Arabia. This study aimed to document medication adherence in Saudi patients with type 2 diabetes. Methods: A quantitative cross-sectional study was conducted in Saudi out-patients with type 2 DM in the city of Khobar, Saudi Arabia. The study used the General Medication Adherence Scale (GMAS) to document medication adherence in this population. Data was analyzed through SPSS version 23. Study was ethically approved. Results: Data was collected from 212 patients. Few patients (35.8%) had high adherence to anti diabetic medications. The correlation between HbA1c level and adherence score was negative and significantly strong (ρ = -0.413, p < 0.0001). Most patients (N = 126, 59.4%) modified their medication therapy during month of Ramadan and on Eid occassion. Education level was not a determinant of adherence in this population. Conclusion: This study highlighted that medication adherence is influenced by religious and social factors. Patient counseling is required to improve patient beliefs and increase awareness of adhering to prescribed anti diabetic pharmacotherapy. A pharmacist can play constructive role of a disease educator and patient counselor.
Fulltext Association of Disease Knowledge and Medication Adherence Among Out-Patients With Type 2 Diabetes Mellitus in Khobar, Saudi Arabia

AlShayban DM, Naqvi AA, Alhumaid O, AlQahtani AS, Islam MA, Ghori SA, et al.

Front Pharmacol, 2020;11:60.
PMID: 32153397 DOI: 10.3389/fphar.2020.00060

Objective: The study aimed to evaluate the association between disease knowledge and medication adherence in patients with type 2 diabetes mellitus.
Methods: A cross-sectional study was conducted for three months, in patients with type 2 diabetes who visited three community pharmacies located in Khobar, Saudi Arabia. Patients' disease knowledge and their adherence to medications were documented using Arabic versions of the Michigan Diabetes Knowledge Test and the General Medication Adherence Scale respectively. Data were analyzed through SPSS version 23. Chi-square test was used to report association of demographics with adherence. Spearman's rank correlation was employed to report the relationship among HbA1c values, disease knowledge and adherence. Logistic regression model was utilized to report the determinants of medication adherence and their corresponding adjusted odds ratio. Study was approved by concerned ethical committee (IRB-UGS-2019-05-001).
Results: A total of 318 patients consented to participate in the study. Mean HbA1c value was 8.1%. A third of patients (N = 105, 33%) had high adherence and half of patients (N = 162, 50.9%) had disease knowledge between 51% - 75%. A significantly weak-to-moderate and positive correlation (ρ = 0.221, p < 0.01) between medication adherence and disease knowledge was reported. Patients with >50% correct answers in the diabetes knowledge test questionnaire were more likely to be adherent to their medications (AOR 4.46, p < 0.01).
Conclusion: Disease knowledge in most patients was average and half of patients had high-to-good adherence. Patients with better knowledge were 4 to 5 times more likely to have high adherence. This highlights the importance of patient education and awareness regarding medication adherence in managing diabetes.
Attitudes, Practices, and Barriers of Malaysian Community Pharmacists Toward Provision of Weight Management Services

Verma RK, Paraidathathu T, Taha NA, Chong WW

Front Pharmacol, 2019;10:138.
PMID: 30873024 DOI: 10.3389/fphar.2019.00138

In Malaysia, sharp increment in the prevalence of obesity over the last four decades has been documented. Community pharmacists (CPs) are strategically placed to tackle obesity by providing weight managements services (WMS) to general public. This study assessed the attitudes, practices and perceived barriers of Malaysian CPs to the provision of WMS. A cross-sectional, descriptive survey was conducted, and responses related to attitudes, practices and perceived barriers of CPs were collected using five-point Likert scale. A total of 550 pharmacists who worked across six states of Malaysia (Selangor, Federal Territory of Kuala Lumpur, Pulau Pinang, Johor, Sabah, and Melaka) participated in this study. Most of the CPs strongly agreed that over eating (n = 312, 56.7%) and sedentary lifestyles (n = 297, 54.0%) contribute to obesity and overweight. Most of them also strongly agreed that exercise training is an effective weight reduction strategy (n = 285, 51.9%), but they were generally not in favor of surgery (n = 231, 42% disagreed/strongly disagreed). CPs generally perceived barriers related to a lack of staff to provide WMS (n = 308, 56.0% agreed/strongly agreed) and ethical and legal issues associated with sales of products/drugs for obesity management (n = 285, 51.9% agreed/strongly agreed). Sociodemographic and practice characteristics such as age group, type of pharmacy, highest education qualification, and employment status of CPs influenced the attitudes, practices and perceived barriers associated with WMS. In terms of age, CPs who were aged less then 30 years expressed significantly stronger agreement that medication adherence is beneficial for weight loss compared to those CPs between 41-50 years. Additionally, CPs who were pharmacy owners provided significantly more frequent BMI measurement and patient information materials as part of their weight management practices compared to CPs who worked as a part timer/locum. This study could be taken as a baseline study on Malaysian CPs' perceptions on WMS.

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