Anti-atherogenic mechanism of ethanol extract of Christia vespertilionis (L.f.) Bakh. F. Leaves in vitro.

BACKGROUND: Vascular inflammation is the key event in early atherogenesis. Pro-inflammatory endothelial cells induce monocyte recruitment into the sub-endothelial layer of the artery. This requires endothelial expression of adhesion molecules namely intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), alongside chemokines production. Christia vespertilionis (L.f.) Bakh.f. (CV) possesses anti-inflammatory property. However, its potential anti-atherogenic effect in the context of vascular inflammation has yet to be explored. PURPOSE: To evaluate the anti-atherogenic mechanism of 80% ethanol extract of CV leaves on tumor necrosis factor-α (TNF-α)-activated human umbilical vein endothelial cells (HUVECs). METHODS: Qualitative analysis of the CV extract was carried out by using liquid chromatography with tandem mass spectrometry (LC-MS/MS). The cell viability of HUVECs treated with CV extract was determined by MTT assay. The effect of CV extract on monocyte adhesion was determined by monocyte-endothelial adhesion assay. Protein expressions of ICAM-1, VCAM-1 and nuclear factor-kappa B (NF-κB) signaling pathway were determined by western blot while production of monocyte chemoattractant protein-1 (MCP-1) was determined by ELISA. RESULTS: LC-MS/MS analysis showed that CV extract composed of five main compounds, including schaftoside, orientin, isovitexin, 6-caffeoyl-D-glucose, and 3,3'-di-O-methyl ellagic acid. Treatment of CV extract at a concentration range from 5 to 60 µg/mL for 24 h maintained HUVECs viability above 90 %, therefore concentrations of 20, 40 and 60 µg/mL were selected for the subsequent experiments. All concentrations of CV extract showed a significant inhibitory effect on monocyte adhesion to TNF-α-activated HUVECs (p < 0.05). In addition, the protein expressions of ICAM-1 and VCAM-1 were significantly attenuated by CV in a concentration dependent manner (p < 0.001). At all tested concentrations, CV extract also exhibited significant inhibition on the production of MCP-1 (p < 0.05). Moreover, CV extract significantly inhibited TNF-α-induced phosphorylation of inhibitor of nuclear factor-κB kinase alpha/beta (IKKα/ß), inhibitor kappa B-alpha (IκBα), NF-κB and nuclear translocation of NF-κB (p < 0.05). CONCLUSION: CV extract inhibited monocyte adhesion to endothelial cells by suppressing protein expressions of cell adhesion molecules and production of chemokines through downregulation of NF-κB signaling pathway. Thus, CV has the potential to be developed as an anti-atherogenic agent for early treatment of atherosclerosis.

Phytochemical profile and diverse pharmacology of Garcinia celebica L.

Garcinia celebica L. syn. Garcinia hombroniana Pierre belongs to the family Clusiaceae, is indigenous to Southeast Asian countries. This review aims to provide updated, comprehensive and categorized information on the phytoconstituents and pharmacological effects of this species. The data collection mainly involved searches through databases named Scopus, Google Scholar, Pubmed and Springer Link. Approximately 100 phytochemicals were recorded in this review, with various classes of compounds such as triterpenoids, flavonoids, benzophenones, xanthones, depsidones and sterols identified. The most abundant compounds isolated belong to two chemical classes: triterpenoids and xanthones. Their extracts and pure compounds have been reported for their antibacterial, antiparasitic, hepatoprotective, antioxidant, antidiabetic, antituberculosis, antiplatelet aggregation, anti-neuraminidase and cholinesterase inhibitory activities. This review will provide a comprehensive understanding between the phytochemical components and its medicinal uses that may serve as a valuable resource for future drug development.

Immunosuppressive Effects of Annona muricata L. Leaf Extract on Cellular and Humoral Immune Responses in Male Wistar Rats.

BACKGROUND: Annona muricata L. (Annonaceae) (AM)'s remarkable anti-inflammatory and anti-cancer activities make it a targeted plant to be explored for its immunomodulatory properties. Traditional practitioners have employed various components of AM to cure a variety of ailments, including cancer, diabetes, and inflammation. OBJECTIVE: The present study evaluated the immunosuppressive effects of 80% ethanol extract of of AM leaves in male Wistar rats on different parameters of humoral and cellular immune responses. METHODS: AM leaf extract (AMLE) was analyzed using UHPLC-MS/MS to profile its secondary metabolites. AMLE was rich in polyphenols which include (epi)catechin-(epi)catechin-(epi) catechin, caffeic acid, coumaroylquinic acid, hyperin, kaempferol, quinic acid and rutin. The rats were administered 100, 200 and 400 mg/kg bw of the extract daily for 14 days. The effects of AMLE on innate immune responses were determined by evaluating phagocytosis, neutrophils migration, reactive oxygen species (ROS) release, CD11b/CD18 integrin expression, and ceruloplasmin, lysozyme and myeloperoxidase (MPO) levels. The adaptive immune parameters were evaluated by immunizing the rats with sheep red blood cells (sRBC) on day 0 and administered orally with AMLE for 14 days. RESULTS: AMLE established significant immunosuppressive effects on the innate immune parameters by inhibiting the neutrophil migration, ROS production, phagocytic activity and expression of CD11b/CD18 integrin in a dose-dependent pattern. AMLE also suppressed ceruloplasmin, MPO and lysozyme expressions in the rat plasma dose-dependently. AMLE dose-dependently inhibited T and B lymphocytes proliferation, Th1 and Th2 cytokine production, CD4+ and CD8+ co-expression in splenocytes, immunoglobulins (IgM and IgG) expression and the sRBC-induced swelling rate of rat paw in delayed-type hypersensitivity (DTH). CONCLUSION: The strong inhibitory effects on the different parameters of humoral and cellular responses indicate that AMLE has potential to be an important source of effective immunosuppressive agents.

Gynura procumbens (Lour.) Merr. extract attenuates monocyte adherence to endothelial cells through suppression of the NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Gynura procumbens (Lour.) Merr. (GP) is a herbaceous plant that grows in Malaysia and other parts of Southeast Asia. The herb is consumed as a remedy for various inflammatory-associated diseases, such as cancer, rheumatism, hypertension, diabetes mellitus and hyperlipidemia. Scientific studies demonstrate that GP extract possesses cardioprotective and anti-inflammatory effects. Cardiovascular disease is mainly caused by atherosclerosis, and inflammation plays a major role in all phases of atherosclerosis. The early inflammatory events in atherogenesis are the activation of endothelial cells and the recruitment of monocytes. AIM OF THE STUDY: This study aimed to evaluate the inhibitory effect of 80% ethanol extract of GP leaves (GPE) on the adherence of monocytes to the activated human endothelial cells and its underlying mechanism. MATERIAL AND METHODS: Qualitative and quantitative analyses of the extract were carried out by using a validated HPLC and UHPLC-MS/MS methods. The MTT test was used to select the range of concentration of extract for this study. The effect of GPE on TNF-α-induced monocyte-endothelial interaction was determined by the in vitro adhesion assay. Expression of cell surface proteins (ICAM-1, VCAM-1) and phosphorylation of nuclear factor kappa B (NF-κB) were determined by western blot, while expression of a chemokine (MCP-1) was identified by an enzyme-linked immunosorbent assay. RESULTS: HPLC and UHPLC-MS/MS analyses indicated that GPE contained chlorogenic acid, nicotiflorin and astragalin as the major compounds. GPE at 20, 40 and 60 µg/mL concentrations showed a significant reduction in monocyte adherence to endothelial cells and expression of ICAM-1 and MCP-1. However, only GPE at concentrations of 40 and 60 µg/mL was able to reduce VCAM-1 expression. Furthermore, GPE significantly inhibited IKKα/ß, IκBα, NF-κB phosphorylation and NF-κB translocation. CONCLUSION: In conclusion, GPE may inhibit monocyte adherence to the activated endothelial cells and expression of ICAM-1, VCAM-1 and MCP-1, which are important proteins for monocyte-endothelial interaction, by suppressing the NF-κB signaling pathway. The results of this study support the traditional use of GPE to counteract inflammation-associated diseases and suggest that GP can be a potential source for bioactive compounds for the development of anti-inflammatory agents to prevent atherosclerosis.

Genistein: A Review on its Anti-Inflammatory Properties.

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.

Pharmacological activities and mechanisms of action of hypophyllanthin: A review.

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.

A new prenylated benzoquinone from Cyathocalyx pruniferus abrogates LPS-induced inflammatory responses associated with PGE2, COX-2 and cytokines biosynthesis in human plasma.

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-1ß 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-1ß 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-1ß (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.

Anti-Allergic Rhinitis Effects of Medicinal Plants and Their Bioactive Metabolites via Suppression of the Immune System: A Mechanistic Review.

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.

Luteolin and apigenin derived glycosides from Alphonsea elliptica abrogate LPS-induced inflammatory responses in human plasma.

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-1ß 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-1ß 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-1ß and IL-6 inhibition at 25 and 50 µM. Isoorientin, orientin, isovitexin, and vitexin showed significant (p < 0.05) and concentration-dependent PGE2 inhibition with IC50 values (µM) of 11.40, 14.71, 17.70 and 20.58 against indomethacin (8.80). Furthermore, isoorientin, orientin, isovitexin, and vitexin produced significant concentration-dependent inhibition with IC50 values (µM) of COX-2: 7.13, 9.51, 12.81, 16.61; IL-1ß 4.80, 6.20, 10.85, 14.51; IL-6: 4.01, 5.90, 11.51 and 14.88 as compared to dexamethasone: 5.29, 2.93, 3.72, respectively (p < 0.05). CONCLUSION: Conclusively, isolated phytoconstituents are reported for the first time from the A. elliptica. Moreover, isovitexin, vitexin orientin and isoorientin abrogated LPS-induced inflammatory responses in human plasma at non-cytotoxic concentrations.

Mechanistic Studies of the Antiallergic Activity of Phyllanthus amarus Schum. & Thonn. and Its Compounds.

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.

Antioxidant and Anti-Inflammatory Effects of Genus Gynura: A Systematic Review.

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.

Xanthine oxidase inhibitory activity of a new isocoumarin obtained from Marantodes pumilum var. pumila leaves.

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.

A Review on the Potential Use of Medicinal Plants From Asteraceae and Lamiaceae Plant Family in Cardiovascular Diseases.

Cardiovascular diseases are one of the most prevalent diseases worldwide, and its rate of mortality is rising annually. In accordance with the current condition, studies on medicinal plants upon their activity on cardiovascular diseases are often being encouraged to be used in cardiovascular disease management, due to the availability of medicinal values in certain dedicated plants. This review was conducted based on two plant families, which are Asteraceae and Lamiaceae, to study on their action in cardiovascular disease relieving activities, to review the relationship between the phytochemistry of Asteraceae and Lamiaceae families and their effect on cardiovascular diseases, and to study their toxicology. The medicinal plants from these plant family groups are collected based on their effects on the mechanisms that affect the cardiovascular-related disease which are an antioxidant activity, anti-hyperlipidemic or hypocholesterolemia, vasorelaxant effect, antithrombotic action, and diuresis effect. In reference to various studies, the journals that conducted in vivo or in vitro experiments, which were used to prove the specific mechanisms, are included in this review. This is to ensure that the scientific value and the phytochemicals of the involved plants can be seen based on their activity. As a result, various plant species from both Asteraceae and Lamiaceae plant family have been identified and collected based on their study that has proven their effectiveness and uses in cardiovascular diseases. Most of the plants have an antioxidant effect, followed by anti-hyperlipidemia, vasorelaxant, antithrombotic, and diuretic effect from the most available to least available studies, respectively. These are the mechanisms that contribute to various cardiovascular diseases, such as heart attack, stroke, coronary heart disease, and hypertension. Further studies can be conducted on these plant species by identifying their ability and capability to be developed into a new drug or to be used as a medicinal plant in treating various cardiovascular diseases.

Anti-hyperuricemic and Anti-inflammatory Effects of Marantodes pumilum as Potential Treatment for Gout.

Marantodes pumilum (Primulaceae) has been used in Malaysian folk medicine to help women regain strength after delivery and for "sickness in the bones." It was previously revealed that its extracts inhibited xanthine oxidase (XO) activity in vitro. The leaves and roots of M. pumilum var. alata (MPA), var. pumila (MPP), and var. lanceolata (MPL) were individually extracted in ethanol (80%). The anti-hyperuricemic activity was initially assessed by XO inhibition with a spectrophotometric in vitro assay. The most active extract was further investigated on hyperuricemic rat model induced by potassium oxonate to determine serum uric acid levels and liver XO effect. The in vitro anti-inflammatory activity was carried out on monosodium urate (MSU) crystal-induced pro-inflammatory cytokines (i.e., interleukin (IL)1α, IL-1ß, IL-6, IL-8, and tumor necrosis factor (TNF)-α) secretion using human peripheral blood mononuclear cells and ELISA technique, and prostaglandin E2 (PGE2)secretion using radioimmunoassay. The active extract was then investigated on gout-induced inflammation with MSU crystals to determine pro-inflammatory cytokines and PGE2 secretion levels in the synovial fluid of rat knee joint. Quantitative analysis using validated HPLC was performed on the extracts to determine presence of bioactive flavonoids. The findings revealed that extract of MPP leaves gave the highest inhibitory activity on XO (IC50 130.5 µg/mL) compared to other extracts tested. However, all extracts possessed significantly lower activity compared to allopurinol (IC50 0.13 µg/mL). Oral administration of MPP leaf extract (200 mg/kg) significantly reduced serum uric acid level in hyperuricemic rats in time-dependent manner to the baseline level and it was as effective as allopurinol (5 mg/kg). The extract also inhibited liver XO activity (25%) compared to allopurinol (45%). In vitro anti-inflammatory assay showed that extract of MPP roots inhibited MSU crystals-induced secretion of IL-1α, IL-1ß, IL-8, TNF-α, and PGE2 with IC50 values of 36, 25, 38, 18, and 46 µg/mL, respectively. Oral administration of the MPP root extract (200 mg/kg) significantly decreased IL-1α, IL-1ß, IL-6, TNF-α, and PGE2 levels in rat's synovial fluid as effective as indomethacin. There were no significant body weight changes of all experimental animals. MPP extracts showed presence of myricetin, quercetin and kaempferol. Myricetin was detected with values of 0.2 and 0.6 mg/g for root and leaf extracts, respectively. The anti-hyperuricemic of MPP leaf and anti-inflammatory of MPP root indicated that MPP may be promising for complementary therapy of gout.

Sinensetin: An Insight on Its Pharmacological Activities, Mechanisms of Action and Toxicity.

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.

In vitro anti-allergic activity of Moringa oleifera Lam. extracts and their isolated compounds.

BACKGROUND: Moringa oleifera Lam. is a commonly used plant in herbal medicine and has various reported bioactivities such as antioxidant, antimicrobial, anticancer and antidiabetes. It is rich in nutrients and polyphenols. The plant also has been traditionally used for alleviating allergic conditions. This study was aimed to examine the anti-allergic activity of M. oleifera extracts and its isolated compounds. METHOD: M. oleifera leaves, seeds and pods were extracted with 80% of ethanol. Individual compounds were isolated using a column chromatographic technique and elucidated based on the nuclear magnetic resonance (NMR) and electrospray ionisation mass spectrometry (ESIMS) spectral data. The anti-allergic activity of the extracts, isolated compounds and ketotifen fumarate as a positive control was evaluated using rat basophilic leukaemia (RBL-2H3) cells for early and late phases of allergic reactions. The early phase was determined based on the inhibition of beta-hexosaminidase and histamine release; while the late phase was based on the inhibition of interleukin (IL-4) and tumour necrosis factor (TNF-α) release. RESULTS: Two new compounds; ethyl-(E)-undec-6-enoate (1) and 3,5,6-trihydroxy-2-(2,3,4,5,6-pentahydroxyphenyl)-4H-chromen-4-one (2) together with six known compounds; quercetin (3), kaempferol (4), ß-sitosterol-3-O-glucoside (5), oleic acid (6), glucomoringin (7), 2,3,4-trihydroxybenzaldehyde (8) and stigmasterol (9) were isolated from M. oleifera extracts. All extracts and the isolated compounds inhibited mast cell degranulation by inhibiting beta-hexosaminidase and histamine release, as well as the release of IL-4 and TNF-α at varying levels compared with ketotifen fumarate. CONCLUSION: The study suggested that M. oleifera and its isolated compounds potentially have an anti-allergic activity by inhibiting both early and late phases of allergic reactions.

Gynura procumbens Standardised Extract Reduces Cholesterol Levels and Modulates Oxidative Status in Postmenopausal Rats Fed with Cholesterol Diet Enriched with Repeatedly Heated Palm Oil.

Gynura procumbens (Lour.) Merr. (GP) has been reported in previous studies to possess antihyperlipidaemic, antioxidative, and cardioprotective properties. This study was aimed to determine the effect of standardised 80% ethanol extract of GP on lipid profiles and oxidative status of hypercholesterolemic rats. Postmenopausal (PM) Sprague-Dawley rats were ovariectomised and fed with 2% cholesterol diet fortified with five times heated palm oil to develop hyperlipidaemia status. Two doses of the extract (250 and 500 mg/kg) and atorvastatin (10 mg/kg) were administered once daily via oral gavage for 24 weeks. Systolic blood pressure (SBP) was increased during the first month in the postmenopausal group and decreased with GP supplementation. Lipid droplets accumulation was shown at the tunica media (TM) area of the aorta in the postmenopausal group and reduced with GP supplementation. Total cholesterol (TC), total triglycerides (TG), low-density lipoprotein (LDL), and malondialdehyde (MDA) levels increased (p < 0.05) at 3 and 6 months in the postmenopausal group and were reduced with GP supplementation. GP also increased high-density lipoprotein (HDL) level in the postmenopausal group. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities were reduced in the postmenopausal group compared to control in the sham group but increased (p < 0.05) with GP supplementation. The results showed that the higher dose of GP (500 mg/kg) gave better effect. GP has the ability to reduce oxidative stress and prevent membrane cell damage through antioxidant enzyme activity modification and lipid profile changes in postmenopausal rats related to atherosclerosis.

Lamiaceae: An Insight on Their Anti-Allergic Potential and Its Mechanisms of Action.

The prevalence of allergic diseases such as asthma, allergic rhinitis, food allergy and atopic dermatitis has increased dramatically in recent decades. Conventional therapies for allergy can induce undesirable effects and hence patients tend to seek alternative therapies like natural compounds. Considering the fact above, there is an urgency to discover potential medicinal plants as future candidates in the development of novel anti-allergic therapeutic agents. The Lamiaceae family, or mint family, is a diverse plant family which encompasses more than 7,000 species and with a cosmopolitan distribution. A number of species from this family has been widely employed as ethnomedicine against allergic inflammatory skin diseases and allergic asthma in traditional practices. Phytochemical analysis of the Lamiaceae family has reported the presence of flavonoids, flavones, flavanones, flavonoid glycosides, monoterpenes, diterpenes, triterpenoids, essential oil and fatty acids. Numerous investigations have highlighted the anti-allergic activities of Lamiaceae species with their active principles and crude extracts. Henceforth, this review has the ultimate aim of compiling the up-to-date (2018) findings of published scientific information about the anti-allergic activities of Lamiaceae species. In addition, the botanical features, medicinal uses, chemical constituents and toxicological studies of Lamiaceae species were also documented. The method employed for data collection in this review was mainly the exploration of the PubMed, Ovid and Scopus databases. Additional research studies were obtained from the reference lists of retrieved articles. This comprehensive summarization serves as a useful resource for a better understanding of Lamiaceae species. The anti-allergic mechanisms related to Lamiaceae species are also reviewed extensively which aids in future exploration of the anti-allergic potential of Lamiaceae species.

Raging the War Against Inflammation With Natural Products.

Over the last few decade Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are the drugs of choice for treating numerous inflammatory diseases including rheumatoid arthritis. The NSAIDs produces anti-inflammatory activity via inhibiting cyclooxygenase enzyme, responsible for the conversation of arachidonic acid to prostaglandins. Likewise, cyclooxegenase-2 inhibitors (COX-2) selectively inhibit the COX-2 enzyme and produces significant anti-inflammatory, analgesic, and anti-pyretic activity without producing COX-1 associated gastrointestinal and renal side effects. In last two decades numerous selective COX-2 inhibitors (COXIBs) have been developed and approved for various inflammatory conditions. However, data from clinical trials have suggested that the prolong use of COX-2 inhibitors are also associated with life threatening cardiovascular side effects including ischemic heart failure and myocardial infection. In these scenario secondary metabolites from natural product offers a great hope for the development of novel anti-inflammatory compounds. Although majority of the natural product based compounds exhibit more selectively toward COX-1. However, the data suggest that slight structural modification can be helpful in developing COX-2 selective secondary metabolites with comparative efficacy and limited side effects. This review is an effort to highlight the secondary metabolites from terrestrial and marine source with significant COX-2 and COX-2 mediated PGE2 inhibitory activity, since it is anticipated that isolates with ability to inhibit COX-2 mediated PGE2 production would be useful in suppressing the inflammation and its classical sign and symptoms. Moreover, this review has highlighted the potential lead compounds including berberine, kaurenoic acid, α-cyperone, curcumin, and zedoarondiol for further development with the help of structure-activity relationship (SAR) studies and their current status.

Demethylbelamcandaquinone B (Dmcq B) Is the Active Compound of Marantodes pumilum var. alata (Blume) Kuntze with Osteoanabolic Activities.

Phytoestrogens have attracted considerable attention for their potential in the prevention of postmenopausal osteoporosis. Recently, a phytoestrogen-rich herbal plant, Marantodes pumilum var. alata (Blume) Kuntze was reported to protect against bone loss in ovariectomized rat. However, the bioactive compound responsible for these effects and the underlying mechanism were not known. Through bioassay-guided isolation, demethylbelamcandaquinone B (Dmcq B) was isolated and identified from Marantodes pumilum var. alata leaf extract. In terms of its bone anabolic effects, Dmcq B was at par with 17ß-estradiol (E2), in promoting the proliferation, differentiation and mineralization of osteoblast cells. Dmcq-B increased early differentiation markers, collagen content and enzymatic ALP activity. It was demonstrated to regulate BMP2 signaling pathway which further activated the transcription factor, osterix. Subsequently, Dmcq B was able to increase the osteocalcin expression which promoted matrix mineralization as evidenced by the increase in calcium deposition. Dmcq B also reduced the protein level of receptor activator of NF-κß ligand (RANKL) and promoted osteoprotegerin (OPG) protein expression by osteoblast cells, therefore hastening bone formation rate by decreasing RANKL/OPG ratio. Moreover, Dmcq B was able to increase ER expression, postulating its phytoestrogen property. As the conclusion, Dmcq B is the active compound isolated from Marantodes pumilum var. alata leaves, regulating osteoanabolic activities potentially through the BMP2 and ER signaling pathways.