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Fulltext Cardioprotective Properties of Kaempferol: A Review

Kamisah Y, Jalil J, Yunos NM, Zainalabidin S

Plants (Basel), 2023 May 24;12(11).
PMID: 37299076 DOI: 10.3390/plants12112096

Cardiac diseases, such as myocardial infarction and heart failure, have become a major clinical problem globally. The accumulating data demonstrate that bioactive compounds with antioxidant and anti-inflammatory properties have favorable effects on clinical problems. Kaempferol is a flavonoid found in various plants; it has demonstrated cardioprotective properties in numerous cardiac injury models. This review aims to collate updated information regarding the effects of kaempferol on cardiac injury. Kaempferol improves cardiac function by alleviating myocardial apoptosis, fibrosis, oxidative stress, and inflammation while preserving mitochondrial function and calcium homeostasis. However, the mechanisms of action of its cardioprotective properties remain unclear; therefore, elucidating its action could provide insight into directions for future studies.
Effects of Quercetin on Cardiac Function in Pressure Overload and Postischemic Cardiac Injury in Rodents: a Systematic Review and Meta-Analysis

Siti HN, Jalil J, Asmadi AY, Kamisah Y

Cardiovasc Drugs Ther, 2022 02;36(1):15-29.
PMID: 33064235 DOI: 10.1007/s10557-020-07100-y

PURPOSE: Cardiac dysfunction can occur as a sequela of a state of prolonged pressure overload and postischemic injury. Flavonoids such as quercetin may be protective against cardiovascular disease. This study aimed to systematically assess the effects of quercetin on cardiac function in pressure overload and postischemia-reperfusion injury in rodents.
METHODS: A systematic search of the literature up to May 2020 was conducted in PubMed, Ovid Medline, EBSCOhost, Scopus, and the Cochrane Library to identify relevant published studies on quercetin and cardiac function using standardized criteria. Meta-analyses were performed on animal studies of pressure overload and ischemia-reperfusion (I/R) injury.
RESULTS: The effects of quercetin on cardiac function in both models were qualitatively reported in 14 studies. The effects of quercetin in four pressure-overload model studies involving 73 rodents and eight I/R-injury model studies involving 120 rodents were quantitatively assessed by meta-analysis. Quercetin improved the overall cardiac function in both pressure overload (n = 4 studies, n = 73 rodents; SMD = - 1.50; 95% CI: - 2.66 to - 0.33; P
Fulltext Genistein: A Review on its Anti-Inflammatory Properties

Goh YX, Jalil J, Lam KW, Husain K, Premakumar CM

Front Pharmacol, 2022;13:820969.
PMID: 35140617 DOI: 10.3389/fphar.2022.820969

Nowadays, non-resolving inflammation is becoming a major trigger in various diseases as it plays a significant role in the pathogenesis of atherosclerosis, asthma, cancer, obesity, inflammatory bowel disease, chronic obstructive pulmonary disease, neurodegenerative disease, multiple sclerosis, and rheumatoid arthritis. However, prolonged use of anti-inflammatory drugs is usually accompanied with undesirable effects and hence more patients tend to seek for natural compounds as alternative medicine. Considering the fact above, there is an urgency to discover and develop potential novel, safe and efficacious natural compounds as drug candidates for future anti-inflammatory therapy. Genistein belongs to the flavonoid family, in the subgroup of isoflavones. It is a phytoestrogen that is mainly derived from legumes. It is a naturally occurring chemical constituent with a similar chemical structure to mammalian estrogens. It is claimed to exert many beneficial effects on health, such as protection against osteoporosis, reduction in the risk of cardiovascular disease, alleviation of postmenopausal symptoms and anticancer properties. In the past, numerous in vitro and in vivo studies have been conducted to investigate the anti-inflammatory potential of genistein. Henceforth, this review aims to summarize the anti-inflammatory properties of genistein linking with the signaling pathways and mediators that are involved in the inflammatory response as well as its toxicity profile. The current outcomes are analysed to highlight the prospect as a lead compound for drug discovery. Data was collected using PubMed, ScienceDirect, SpringerLink and Scopus databases. Results showed that genistein possessed strong anti-inflammatory activities through inhibition of various signaling pathways such as nuclear factor kappa-B (NF-κB), prostaglandins (PGs), inducible nitric oxide synthase (iNOS), proinflammatory cytokines and reactive oxygen species (ROS). A comprehensive assessment of the mechanism of action in anti-inflammatory effects of genistein is included. However, evidence for the pharmacological effects is still lacking. Further studies using various animal models to assess pharmacological effects such as toxicity, pharmacokinetics, pharmacodynamics, and bioavailability studies are required before clinical studies can be conducted. This review will highlight the potential use of genistein as a lead compound for future drug development as an anti-inflammatory agent.
Fulltext Pharmacological activities and mechanisms of action of hypophyllanthin: A review

Wan Saidin WA, Jantan I, Abdul Wahab SM, Jalil J, Mohd Said M, Yusoff SD, et al.

Front Pharmacol, 2022;13:1070557.
PMID: 36699081 DOI: 10.3389/fphar.2022.1070557

Hypophyllanthin is a major lignan present in various Phyllanthus species and has been used as one of the bioactive chemical markers for quality control purposes as it contributes to their diverse pharmacological activities. The objective of this study is to compile up-to-date data on the pharmacological actions and mechanisms of hypophyllanthin. This review also includes the extracts of Phyllanthus species whose pharmacological actions have been partially attributed to hypophyllanthin. The scientific findings on the compound are critically analyzed and its potential as a lead molecule for the discovery of drug candidates for the development of therapeutics to treat diverse diseases is highlighted. Data collection was mainly through the exploration of Ovid-MEDLINE, Scopus, Science Direct, and Elsevier databases. Studies conducted in vitro and in vivo showed that hypophyllanthin had potent immunomodulating properties as well as a variety of other pharmacological properties, including anti-inflammatory, hepatoprotective, anti-tumor, anti-allergic, anti-hypertensive, and phytoestrogenic properties. Several mechanisms of action on the effects of hypophyllanthin on the immune system, in cancer and other disease states, were presented to provide some insights into its pharmacological effects. Before being submitted to clinical investigations, additional animal studies utilising different animal models are necessary to analyse its bioavailability, pharmacokinetics, and pharmacodynamic properties, as well as its toxicity, to determine its efficacy and safety. Understanding its potential as a lead molecule for the discovery of therapeutic candidates, particularly for the development of therapies for inflammatory and immune-related disorders, requires an understanding of its pharmacological activities and mechanisms of action. An insight into its pharmacological activities and mechanisms of action will provide an understanding of its potential as a lead compound for the discovery of drug candidates, especially for the development of therapies for inflammatory and immune related diseases.
Luteolin and apigenin derived glycosides from Alphonsea elliptica abrogate LPS-induced inflammatory responses in human plasma

Attiq A, Jalil J, Husain K, Mohamad HF, Ahmad A

J Ethnopharmacol, 2021 Jul 15;275:114120.
PMID: 33857595 DOI: 10.1016/j.jep.2021.114120

ETHNOPHARMACOLOGICAL RELEVANCE: Numerous Alphonsea species including Alphonsea elliptica (mempisang) leaves and fruits are indigenously used in inflammatory conditions such as postpartum swelling and rheumatism in southeast Asian countries. In our previous in-vitro findings, A. elliptica methanol extract exhibited platelet-activating factor inhibition, suggesting the presence of phyto-constituents with anti-inflammatory potential.
AIM OF THE STUDY: However, so far there is no literature available on the anti-inflammatory activity of this species. Henceforth, based on the above background and our previous laboratory findings, we hypothesize that phytoconstituents of A. elliptica could possess anti-inflammatory potential against inflammatory mediators including prostaglandin-E2 (PGE2), cyclooxegenase-2 (COX-2) and cytokines (IL-1β and IL-6).
MATERIALS AND METHODS: Vacuum and column chromatography techniques were employed for the isolation of phytoconstituents. The structure elucidation was carried out using HRESI-MS, 1H and 13C-NMR analysis and compared with the published literature. For cytotoxicity analysis, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed on peripheral blood mononuclear cells. In-vitro anti-inflammatory activities were evaluated against the levels of PGE2, COX-2, IL-1β and IL-6 in lipopolysaccharide (LPS)-induced human plasma using enzyme-linked immunosorbent assay and radioimmunoassay.
RESULTS: Unprecedentedly, chromatographic purification of methanolic leaves extract afforded five flavones namely vitexin, isovitexin, orientin, isoorientin, schaftoside with three flavanols; kaempferol, myricetin and rutin from A elliptica. In cell viability analysis, isolates did not present cytotoxicity up to 50 μM. In anti-inflammatory evaluation, orientin and isoorientin exhibited strong (≥70%), while isovitexin and vitexin produced strong to moderate (50-69%) PGE2, COX-2, IL-1β and IL-6 inhibition at 25 and 50 μM. Isoorientin, orientin, isovitexin, and vitexin showed significant (p
A new prenylated benzoquinone from Cyathocalyx pruniferus abrogates LPS-induced inflammatory responses associated with PGE2, COX-2 and cytokines biosynthesis in human plasma

Attiq A, Jalil J, Husain K, Jamal JA, Ismail EN

Inflammopharmacology, 2021 Jun;29(3):841-854.
PMID: 33864564 DOI: 10.1007/s10787-021-00807-w

In our previous laboratory findings, Cyathocalyx pruniferus extracts exhibited platelet-activating factor inhibition, suggesting their anti-inflammatory potential. Hence, this study was designed with the aim to isolate phyto-constituents from C. pruniferus with potent anti-inflammatory activities. Column and volume liquid chromatography were used for isolation of phyto-constituents. The structure elucidation was carried out using spectroscopic analysis (HRESI-MS, 1H and 13C-NMR) and compared with published literature. For cytotoxicity analysis, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide assay was performed on peripheral blood mononuclear cells. Anti-inflammatory activities were evaluated against the levels of inflammatory cytokines (IL-1β and IL-6), prostaglandin-E2 (PGE2) and cyclooxegenase-2 (COX-2), in lipopolysaccharide (LPS)-induced human plasma using ELISA and radioimmunoassay (RIA). The chromatographic purification of methanol leaves extract afforded 13 (1-13) secondary metabolites. Additionally, cytotoxicity analysis suggested that isolates were non-cytotoxic at 100 μM. In anti-inflammatory evaluation, 2-octaprenyl-1, 4-benzoquinone (5) produced strong (≥ 70%) inhibition of PGE2, COX-2, IL-1β and IL-6 at 50 µM. Moreover, 2-octaprenyl-1,4-benzoquinone (5) exhibited concentration-dependent inhibition with IC50 values (µM) of 11.21, 6.61, 2.20 and 3.56 as compared to controls; indomethacin for PGE2 (11.84) and dexamethasone in COX-2 (5.19), IL-1β (1.83) and IL-6 (3.76) analysis, respectively. In conclusion, two new compounds including 2-octaprenyl-1, 4-benzoquinone (5) and 14-methyloctadec-1-ene (6) are reported for the first time from plant species. Additionally, 2-octaprenyl-1, 4-benzoquinone (5) dose-dependently suppressed the production of pro-inflammatory mediators involved in acute and chronic inflammation at non-cytotoxic concentrations.
Fulltext Rutin Modulates MAPK Pathway Differently from Quercetin in Angiotensin II-Induced H9c2 Cardiomyocyte Hypertrophy

Siti HN, Jalil J, Asmadi AY, Kamisah Y

Int J Mol Sci, 2021 May 11;22(10).
PMID: 34064664 DOI: 10.3390/ijms22105063

Rutin is a flavonoid with antioxidant property. It has been shown to exert cardioprotection against cardiomyocyte hypertrophy. However, studies regarding its antihypertrophic property are still lacking, whether it demonstrates similar antihypertrophic effect to its metabolite, quercetin. Hence, this study aimed to investigate the effects of both flavonoids on oxidative stress and mitogen-activated protein kinase (MAPK) pathway in H9c2 cardiomyocytes that were exposed to angiotensin II (Ang II) to induce hypertrophy. Cardiomyocytes were exposed to Ang II (600 nM) with or without quercetin (331 μM) or rutin (50 μM) for 24 h. A group given vehicle served as the control. The concentration of the flavonoids was chosen based on the reported effective concentration to reduce cell hypertrophy or cardiac injury in H9c2 cells. Exposure to Ang II increased cell surface area, intracellular superoxide anion level, NADPH oxidase and inducible nitric oxide synthase activities, and reduced cellular superoxide dismutase activity and nitrite level, which were similarly reversed by both rutin and quercetin. Rutin had no significant effects on phosphorylated proteins of extracellular signal-related kinases (ERK1/2) and p38 but downregulated phosphorylated c-Jun N-terminal kinases (JNK1/2), which were induced by Ang II. Quercetin, on the other hand, had significantly downregulated the phosphorylated proteins of ERK1/2, p38, and JNK1/2. The quercetin inhibitory effect on JNK1/2 was stronger than the rutin. In conclusion, both flavonoids afford similar protective effects against Ang II-induced cardiomyocyte hypertrophy, but they differently modulate MAPK pathway.
Fulltext Mechanistic Studies of the Antiallergic Activity of Phyllanthus amarus Schum. & Thonn. and Its Compounds

Abd Rani NZ, Lam KW, Jalil J, Mohamad HF, Mat Ali MS, Husain K

Molecules, 2021 Jan 28;26(3).
PMID: 33525733 DOI: 10.3390/molecules26030695

Phyllanthus amarus Schum. & Thonn. (Phyllanthaceae) is a medicinal plant that is commonly used to treat diseases such as asthma, diabetes, and anemia. This study aimed to examine the antiallergic activity of P. amarus extract and its compounds. The antiallergic activity was determined by measuring the concentration of allergy markers release from rat basophilic leukemia (RBL-2H3) cells with ketotifen fumarate as the positive control. As a result, P. amarus did not stabilize mast cell degranulation but exhibited antihistamine activity. The antihistamine activity was evaluated by conducting a competition radioligand binding assay on the histamine 1 receptor (H1R). Four compounds were identified from the high performance liquid chromatography (HPLC) analysis which were phyllanthin (1), hypophyllanthin (2), niranthin (3), and corilagin (4). To gain insights into the binding interactions of the most active compound hypophyllanthin (2), molecular docking was conducted and found that hypophyllanthin (2) exhibited favorable binding in the H1R binding site. In conclusion, P. amarus and hypophyllanthin (2) could potentially exhibit antiallergic activity by preventing the activation of the H1 receptor.
Fulltext UPLC-MS-Based Metabolomics Profiling for α-Glucosidase Inhibiting Property of Parkia speciosa Pods

Saleh MSM, Jalil J, Mustafa NH, Ramli FF, Asmadi AY, Kamisah Y

Life (Basel), 2021 Jan 22;11(2).
PMID: 33499128 DOI: 10.3390/life11020078

Parkia speciosa is a food plant that grows indigenously in Southeast Asia. A great deal of interest has been paid to this plant due to its traditional uses in the treatment of several diseases. The pods contain many beneficial secondary metabolites with potential applications in medicine and cosmetics. However, studies on their phytochemical properties are still lacking. Therefore, the present study was undertaken to profile the bioactive compounds of P. speciosa pods collected from six different regions of Malaysia through ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) and α-glucosidase inhibitory potential. This study applied metabolomics to elucidate the differences between P. speciosa populations found naturally in the different locations and to characterize potential α-glucosidase inhibitors from P. speciosa pods. P. speciosa collected from different regions of Malaysia showed good α-glucosidase inhibitory activity, with a median inhibitory concentration (IC50) of 0.45-0.76 μg/mL. The samples from the northern and northeastern parts of Peninsular Malaysia showed the highest activity. Using UHPLC-QTOF-MS/MS analysis, 25 metabolites were identified in the pods of P. speciosa. The findings unveiled that the pods of P. speciosa collected from different locations exhibit different levels of α-glucosidase inhibitory activity. The pods are a natural source of potent antidiabetic bioactive compounds.
Fulltext Genus Parkia: Phytochemical, Medicinal Uses, and Pharmacological Properties

Saleh MSM, Jalil J, Zainalabidin S, Asmadi AY, Mustafa NH, Kamisah Y

Int J Mol Sci, 2021 Jan 09;22(2).
PMID: 33435507 DOI: 10.3390/ijms22020618

The genus Parkia (Fabaceae, Subfamily, Mimosoideae) comprises about 34 species of mostly evergreen trees widely distributed across neotropics, Asia, and Africa. This review aims to provide an overview of the current status of the species from the genus Parkia in terms of its relationship between its phytochemistry and medical uses. Comprehensive information on Parkia species was retrieved from electronic databases, which were Web of Science, ScienceDirect, PubMed, and Google Scholar. This review identified nine species from genus Parkia with properties of medicinal use. They are used traditionally to treat several ailments, such as diabetes, diarrhea, wounds, hypertension, cough, chronic piles, conjunctivitis, and measles. The most common species studied are P. biglobosa, P. speciosa, P. javanica, P. bicolor, P. biglandulosa, P. filicoidea, and P. clappertoniana. A considerable number of secondary metabolites, such as terpenoids, phenolic acids, flavonoids (aglycone and glycosides), and numerous volatile compounds have been identified in this genus, which are responsible for their diverse pharmacological activities. Their extracts, pure compounds and seed lectins have been reported for their anticancer, antimicrobial, antihypertensive, antiulcer, antidiabetic, anti-inflammatory, antioxidant, antimalarial, hepatoprotective, and antidiarrheal activities. The information gathered in this review might be of help for future studies in terms of the current knowledge on the link between the phytochemical components and medicinal uses. This could facilitate more discoveries on its potentials particularly in the pharmacological characteristics and potential to be developed into modern medicines.
Fulltext Parkia speciosa Hassk. Empty Pod Extract Alleviates Angiotensin II-Induced Cardiomyocyte Hypertrophy in H9c2 Cells by Modulating the Ang II/ROS/NO Axis and MAPK Pathway

Siti HN, Jalil J, Asmadi AY, Kamisah Y

Front Pharmacol, 2021;12:741623.
PMID: 34721028 DOI: 10.3389/fphar.2021.741623

Cardiac hypertrophy is characteristic of heart failure in patients who have experienced cardiac remodeling. Many medicinal plants, including Parkia speciosa Hassk., have documented cardioprotective effects against such pathologies. This study investigated the activity of P. speciosa empty pod extract against cardiomyocyte hypertrophy in H9c2 cardiomyocytes exposed to angiotensin II (Ang II). In particular, its role in modulating the Ang II/reactive oxygen species/nitric oxide (Ang II/ROS/NO) axis and mitogen-activated protein kinase (MAPK) pathway was examined. Treatment with the extract (12.5, 25, and 50 μg/ml) prevented Ang II-induced increases in cell size, NADPH oxidase activity, B-type natriuretic peptide levels, and reactive oxygen species and reductions in superoxide dismutase activity. These were comparable to the effects of the valsartan positive control. However, the extract did not significantly ameliorate the effects of Ang II on inducible nitric oxide synthase activity and nitric oxide levels, while valsartan did confer such protection. Although the extract decreased the levels of phosphorylated extracellular signal-related kinase, p38, and c-Jun N-terminal kinase, valsartan only decreased phosphorylated c-Jun N-terminal kinase expression. Phytochemical screening identified the flavonoids rutin (1) and quercetin (2) in the extract. These findings suggest that P. speciosa empty pod extract protects against Ang II-induced cardiomyocyte hypertrophy, possibly by modulating the Ang II/ROS/NO axis and MAPK signaling pathway via a mechanism distinct from valsartan.
Fulltext Extracts of Andrographis paniculata (Burm.f.) Nees Leaves Exert Anti-Gout Effects by Lowering Uric Acid Levels and Reducing Monosodium Urate Crystal-Induced Inflammation

Rahmi EP, Kumolosasi E, Jalil J, Buang F, Jamal JA

Front Pharmacol, 2021;12:787125.
PMID: 35095497 DOI: 10.3389/fphar.2021.787125

Andrographis paniculata (Burm.f.) Nees has been found to have anti-inflammatory and immunostimulatory effects. This study was to investigate antihyperuricemic and anti-inflammatory effects of A. paniculata leaf extracts. Andrographolide, 14-deoxy-11,12-didehydroandrographolide, and neoandrographolide were quantified in 80% ethanol (EtOH80) and water extracts using High Performance Liquid Chromatography (HPLC) analysis. Antihyperuricemic activity was evaluated using a spectrophotometric in vitro inhibitory xanthine oxidase (XO) assay. The most active extract and andrographolide were further investigated in a hyperuricemic rat model induced by potassium oxonate to determine serum uric acid levels, liver XO activity, followed by Western blot analysis for renal urate transporter URAT1, GLUT9, and OAT1 to investigate the excretion of uric acid via kidney. Anti-inflammatory activity was assessed by in vitro interleukin assay for interleukin (IL-1α, IL-1β, IL-6, IL-8), and tumor necrosis factor (TNF-α) in monosodium urate (MSU) crystal-induced human fibroblast-like synoviocyte (HFLS) cells using ELISA-kits, followed by Western blot analysis for the expression of MyD88, NLRP3, NF-κB p65, and caspase-1 proteins to investigate the inflammation pathway. In vivo assay of the most active extract and andrographolide were performed based on the swelling rate and inhibition of pro-inflammatory mediator release from synovial fluid of a rat knee joint induced by MSU crystals. The results showed that the EtOH80 extract had a greater amount of andrographolide (11.34% w/w) than the water extract (1.38% w/w). In the XO inhibitory activity, none of the samples exhibited greater than 50% inhibition. However, in a rat model, EtOH80 extract (200 mg/kg/day) and andrographolide (30 mg/kg/day) decreased serum uric acid levels and reduced liver XO activity, reduced the protein expression levels of URAT1 and GLUT9, and restored the decrease in OAT1 levels. In the in vitro anti-inflammatory study, EtOH80 extract and andrographolide significantly decreased production of IL-1α, IL-1β, IL-6, and TNF-α, as well as inhibited the synthesis of MyD88, NLRP3, NF-κB p65, and caspase-1 in a concentration-dependent manner, almost comparable to dexamethasone. The EtOH80 extract (200 mg/kg/day) and andrographolide (30 mg/kg) significantly decreased swelling rate and IL-1α, IL-1β, IL-6, and TNF-α in the synovial fluid of rat models in a time-dependent manner, comparable to indomethacin (3 mg/kg/day). In conclusion, the findings show that EtOH80 extract has a substantial anti-gout effect by lowering uric acid levels and suppressing pro-inflammatory mediator production due to the andrographolide content, that might be beneficial in the treatment of gouty-inflammation.
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 Xanthine oxidase inhibitory activity of a new isocoumarin obtained from Marantodes pumilum var. pumila leaves

Aladdin NA, Husain K, Jalil J, Sabandar CW, Jamal JA

BMC Complement Med Ther, 2020 Oct 27;20(1):324.
PMID: 33109178 DOI: 10.1186/s12906-020-03119-8

BACKGROUND: In traditional Malay medicine, Marantodes pumilum (Blume) Kuntze (family Primulaceae) is commonly used by women to treat parturition, flatulence, dysentery, dysmenorrhea, gonorrhea, and bone diseases. Preliminary screening of some Primulaceae species showed that they possess xanthine oxidase inhibitory activity. Thus, this study aimed to investigate the xanthine oxidase inhibitory activity of three varieties of M. pumilum and their phytochemical compounds.
METHOD: Dichloromethane, methanol, and water extracts of the leaves and roots of M. pumilum var. alata, M. pumilum var. pumila, and M. pumilum var. lanceolata were tested using an in vitro xanthine oxidase inhibitory assay. Bioassay-guided fractionation and isolation were carried out on the most active extract using chromatographic techniques. The structures of the isolated compounds were determined using spectroscopic techniques.
RESULTS: The most active dichloromethane extract of M. pumilum var. pumila leaves (IC50 = 161.6 μg/mL) yielded one new compound, 3,7-dihydroxy-5-methoxy-4,8-dimethyl-isocoumarin (1), and five known compounds, viz. ardisiaquinone A (2), maesanin (3), stigmasterol (4), tetracosane (5), and margaric acid (6). The new compound was found to be the most active xanthine oxidase inhibitor with an IC50 value of 0.66 ± 0.01 μg/mL, which was not significantly different (p > 0.05) from that of the positive control, allopurinol (IC50 = 0.24 ± 0.00 μg/mL).
CONCLUSION: This study suggests that the new compound 3,7-dihydroxy-5-methoxy-4,8-dimethyl-isocoumarin (1), which was isolated from the dichloromethane extract of M. pumilum var. pumila leaves, could be a potential xanthine oxidase inhibitor.
Modulation of inflammatory pathways, medicinal uses and toxicities of Uvaria species: potential role in the prevention and treatment of inflammation

Jalil J, Attiq A, Hui CC, Yao LJ, Zakaria NA

Inflammopharmacology, 2020 Oct;28(5):1195-1218.
PMID: 32617790 DOI: 10.1007/s10787-020-00734-2

The therapeutic efficacy of the contemporary anti-inflammatory drugs are well established; however, prolonged use of such can often lead to serious and life-threatening side effects. Natural product-based anti-inflammatory compounds with superior efficacy and minimum toxicity can serve as possible therapeutic alternatives in this scenario. Genus Uvaria is a part of Annonaceae family, while the majority of its species are widely distributed in tropical rain forest regions of South East Asia. Uvaria species have been used extensively used as traditional medicine for treating all sorts of inflammatory diseases including catarrhal inflammation, rheumatism, acute allergic reactions, hemorrhoids, inflammatory liver disease and inflamed joints. Phytochemical analysis of Uvaria species has revealed flavones, flavonoids, tannins, saponins, polyoxygenated cyclohexene and phenolic compounds as major phyto-constituents. This review is an attempt to highlight the anti-inflammatory activity of Uvaria species by conducting a critical appraisal of the published literature. The ethnopharmacological relevance of Uvaria species in the light of toxicological studies is also discussed herein. An extensive and relevant literature on anti-inflammatory activity of Uvaria species was collected from available books, journals and electronic databases including PubMed, ScienceDirect, Scopus, Proquest and Ovid. Extracts and isolates of Uvaria species exhibited significant anti-inflammatory activity through various mechanisms of action. 6,7-di-O-Methyl-baicalein, flexuvarol B, chrysin, (-)-zeylenol, 6-hydroxy-5,7-dimethoxy-flavone, and pinocembrin were the most potent anti-inflammatory compounds with comparable IC50 with positive controls. Therefore, it is suggested that further research should be carried out to determine the pharmacokinetics, pharmacodynamics and toxicity of these therapeutically significant compounds, to convert the pre-clinical results into clinical data for drug development and design.
Profiling of gene expression in methicillin-resistant Staphylococcus aureus in response to cyclo-(L-Val-L-Pro) and chloramphenicol isolated from Streptomyces sp., SUK 25 reveals gene downregulation in multiple biological targets

Zin NM, Al-Shaibani MM, Jalil J, Sukri A, Al-Maleki AR, Sidik NM

Arch Microbiol, 2020 Oct;202(8):2083-2092.
PMID: 32494868 DOI: 10.1007/s00203-020-01896-x

Chloramphenicol (CAP) and cyclo-(L-Val-L-Pro) were previously isolated from Streptomyces sp., SUK 25 which exhibited a high potency against methicillin-resistant Staphylococcus aureus (MRSA). This study aimed to profile gene expression of MRSA treated with CAP and cyclo-(L-Val-L-Pro) compounds using DNA microarray. Treatment of MRSA with CAP resulted in upregulation of genes involved in protein synthesis, suggesting the coping mechanism of MRSA due to the inhibition of protein synthesis effect from CAP. Most upregulated genes in cyclo-(L-Val-L-Pro) were putative genes with unknown functions. Interestingly, genes encoding ribosomal proteins, cell membrane synthesis, DNA metabolism, citric acid cycle and virulence were downregulated in MRSA treated with cyclo-(L-Val-L-Pro) compound, suggesting the efficacy of this compound in targeting multiple biological pathways. Contrary to CAP, with only a single target, cyclo-(L-Val-L-Pro) isolated from this study had multiple antimicrobial targets that can delay antibiotic resistance and hence is a potential antimicrobial agent of MRSA.
Fulltext Performance comparison of EasyFix G26 and HYDRASYS 2 SCAN for the detection of serum monoclonal proteins

Amin Nordin FD, Mohd Khalid MKN, Abdul Aziz SM, Mohamad Bakri NA, Ahmad Ridzuan SN, Abdul Jalil J, et al.

J Clin Lab Anal, 2020 Jun;34(6):e23254.
PMID: 32141626 DOI: 10.1002/jcla.23254

BACKGROUND: Serum protein electrophoresis (SPE) is a widely used laboratory technique to diagnose patients with multiple myeloma (MM) and other disorders related to serum protein. In patients with MM, abnormal monoclonal protein can be detected by SPE and further characterized using immunofixation electrophoresis (IFE). There are several semi-automated agarose gel-based systems available commercially for SPE and IFE. In this study, we sought to evaluate the analytical performance of fully automated EasyFix G26 (EFG26) and semi-automated HYDRASYS 2 SCAN (H2SCAN) for both SPE and IFE.
METHODS: Both instruments were operated according to manufacturer's instructions. Samples used include a commercially available normal control serum (NCS) and patients' specimens. The following were evaluated: precision and comparison studies for SPE, and reproducibility and comparison studies for IFE. Statistical analyses were performed using Microsoft Excel.
RESULTS: For SPE repeatability study, our results showed that EFG26 has higher coefficient of variation (%CV) compared with H2SCAN for both samples except for monoclonal component with %CV of 0.97% and 1.18%, respectively. Similar results were obtained for SPE reproducibility study except for alpha-1 (4.16%) and beta (3.13%) fractions for NCS, and beta fractions (5.36%) for monoclonal sample. Subsequently, reproducibility for IFE was 100% for both instruments. Values for correlation coefficients between both instruments ranged from 0.91 to 0.98 for the five classic bands.
CONCLUSION: Both instruments demonstrated good analytical performance characterized by high precision, reproducibility and correlation.
Fulltext Sinensetin: An Insight on Its Pharmacological Activities, Mechanisms of Action and Toxicity

Han Jie L, Jantan I, Yusoff SD, Jalil J, Husain K

Front Pharmacol, 2020;11:553404.
PMID: 33628166 DOI: 10.3389/fphar.2020.553404

Sinensetin, a plant-derived polymethoxylated flavonoid found in Orthosiphon aristatus var. aristatus and several citrus fruits, has been found to possess strong anticancer activities and a variety of other pharmacological benefits and promising potency in intended activities with minimal toxicity. This review aims to compile an up-to-date reports of published scientific information on sinensetin pharmacological activities, mechanisms of action and toxicity. The present findings about the compound are critically analyzed and its prospect as a lead molecule for drug discovery is highlighted. The databases employed for data collection are mainly through Google Scholar, PubMed, Scopus and Science Direct. In-vitro and in-vivo studies showed that sinensetin possessed strong anticancer activities and a wide range of pharmacological activities such as anti-inflammatory, antioxidant, antimicrobial, anti-obesity, anti-dementia and vasorelaxant activities. The studies provided some insights on its several mechanisms of action in cancer and other disease states. However, more detail mechanistic studies are needed to understand its pharmacological effects. More in vivo studies in various animal models including toxicity, pharmacokinetic, pharmacodynamic and bioavailability studies are required to assess its efficacy and safety before submission to clinical studies. In this review, an insight on sinensetin pharmacological activities and mechanisms of action serves as a useful resource for a more thorough and comprehensive understanding of sinensetin as a potential lead candidate for drug discovery.
Parkia speciosa empty pod extract exerts anti-inflammatory properties by modulating NFκB and MAPK pathways in cardiomyocytes exposed to tumor necrosis factor-α

Gui JS, Jalil J, Jubri Z, Kamisah Y

Cytotechnology, 2019 Feb;71(1):79-89.
PMID: 30600464 DOI: 10.1007/s10616-018-0267-8

Parkia speciosa Hassk is a plant found abundantly in the Southeast Asia region. Its seeds, with or without pods, have been used in traditional medicine locally to treat cardiovascular problems. The pathogenesis of cardiovascular diseases involves inflammation and oxidative stress. Based on this information, we sought to investigate the potential protective effects of Parkia speciosa empty pod extract (PSE) on inflammation in cardiomyocytes exposed to tumor necrosis factor-α (TNF-α). H9c2 cardiomyocytes were divided into four groups; negative control, TNF-α, PSE + TNF-α and quercetin + TNF-α. Groups 3 and 4 were pretreated with PSE ethyl acetate fraction of ethanol extract (500 µg/mL) or quercetin (1000 µM, positive control) for 1 h before inflammatory induction with TNF-α (12 ng/mL) for 24 h. TNF-α increased protein expression of nuclear factor kappa B cell (NFκB) p65, p38 mitogen-activated protein kinase (p38 MAPK), inducible nitric oxide synthase, cyclooxygenase-2 and vascular cell adhesion molecule-1 when compared to the negative control (p
The Medicinal Uses, Toxicities and Anti-inflammatory Activity of Polyalthia Species (Annonaceae)

Yao LJ, Jalil J, Attiq A, Hui CC, Zakaria NA

J Ethnopharmacol, 2018 Oct 11.
PMID: 30316887 DOI: 10.1016/j.jep.2018.10.001

ETHNOPHARMACOLOGICAL RELEVANCE: Polyalthia is one of the largest and notable genera in Annonaceae family. Polyalthia species have been widely used in folklore medicine for the treatment of rheumatic fever, gastrointestinal ulcer and generalized body pain. Numerous in vitro and in vivo studies on Polyalthia Species have also corroborated the significant anti-inflammatory potential of its extracts and secondary metabolites.
AIM OF THE STUDY: This review is an attempt to assess the anti-inflammatory activity of Polyalthia species by giving critical appraisal and establishing evidences of their traditional uses. Moreover this review will highlight the lead compounds for future drug development that can serve as a potential anti-inflammatory drug with comparative efficacy and minimum side effects.
MATERIALS AND METHODS: An extensive literature review, focusing the anti-inflammatory potential of Polyalthia species was conducted using the following databases: PubMed, ScienceDirect, SpringerLink, Ovid, Scopus and ProQuest, as well as the locally available books, journals and relevant documents. The reference lists of retrieved papers were also searched for additional studies.
RESULTS: The Polyalthia species have shown significant anti-inflammatory activity through various mechanism of action. The most significant anti-inflammatory mechanism includes the inhibition of nuclear factor kappa B (NF-κB), prostaglandins (PGs), pro-inflammatory cytokines, inducible nitric oxide synthase (iNOS) and reactive oxygen species (ROS). The data suggests that hydroxycleroda-3,13-dien-15,16-olide and 16-oxocleroda-3,13-dien-15-oic acid, quercetin, rutin, spinasterol, α-spinasterol, goniothalamin and (-)-5-hydroxygoniothalamin are the most potent anti-inflammatory compounds from Polyalthia species with comparable IC50 with positive controls.
CONCLUSIONS: Numerous pharmacological studies have supported the use of Polyalthia species against pain, rheumatic fever, haemorrhages and inflammation in traditional medicine. Flavonoids, diterpenoids, sterols and styrylpyrones from genus Polyalthia are the most significant class of compounds with potent anti-inflammatory activity. Secondary metabolites from these classes should be brought into further research to fill the gaps of knowledge in pharmacokinetics, pharmacodynamics, bioavailability, and toxicity in order to convert the pre-clinical results into clinical data for further investigation.

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