The Antimalarial Effect of Curcumin Is Mediated by the Inhibition of Glycogen Synthase Kinase-3β

Amatul Hamizah Ali,Suhaini Sudi,Rusliza Basir,Noor Embi,Hasidah Mohd Sidek 한국식품영양과학회 2017 Journal of medicinal food Vol.20 No.2

Curcumin, a bioactive compound in Curcuma longa, exhibits various pharmacological activities, including antimalarial effects. In silico docking simulation studies suggest that curcumin possesses glycogen synthase kinase-3β (GSK3β)-inhibitory properties. The involvement of GSK3 in the antimalarial effects in vivo is yet to be demonstrated. In this study, we aimed to evaluate whether the antimalarial effects of curcumin involve phosphorylation of host GSK3β. Intraperitoneal administration of curcumin into Plasmodium berghei NK65-infected mice resulted in dose-dependent chemosuppression of parasitemia development. At the highest dose tested (30 mg/kg body weight), both therapeutic and prophylactic administrations of curcumin resulted in suppression exceeding 50% and improved median survival time of infected mice compared to control. Western analysis revealed a 5.5-fold (therapeutic group) and 1.8-fold (prophylactic group) increase in phosphorylation of Ser 9 GSK3β and 1.6-fold (therapeutic group) and 1.7-fold (prophylactic group) increase in Ser 473 Akt in liver of curcumin-treated infected animals. Following P. berghei infection, levels of pro- and anti-inflammatory cytokines, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-10, and IL-4 were elevated by 7.5-, 35.0-, 33.0-, and 2.2-fold, respectively. Curcumin treatment (therapeutic) caused a significant decrease (by 6.0- and 2.0-fold, respectively) in serum TNF-α and IFN-γ level, while IL-10 and IL-4 were elevated (by 1.4- and 1.8-fold). Findings from the present study demonstrate for the first time that the antimalarial action of curcumin involved inhibition of GSK3β.

An Investigation of the Anti-Inflammatory and Analgesic Effects of Orthosiphon stamineus Leaf Extract

Mun Fei Yam,Mohd. Zaini Asmawi,Rusliza Basir 한국식품영양과학회 2008 Journal of medicinal food Vol.11 No.2

Anti-inflammatory and analgesic activities of a standardized Orthosiphon stamineusmethanol:water (50:50vol/vol) leaf extract (SEOS) were evaluated in animal models. Oral administration of SEOS at doses of 500 and 1,000 mg/kgsignificantly reduced the hind paw edema in rats at 3 and 5 hours after carrageenan administration (P. .01 and P. .01; P..01 and P. .05, respectively). SEOS (1,000 mg/kg, p.o.) also produced significant (P. .05) analgesic activity in both theacetic acid-induced writhing test and the formalin-induced licking test (late phase) in mice and rats, respectively. However,SEOS showed no effect on the tail flick and hot plate tests in mice. The results of the present study support the proposal thatO. stamineushas anti-inflammatory and non-narcotic analgesic activities. These findings justify the traditional use of the plantfor treating pain and inflammation.

A Simple Isocratic HPLC Method for the Simultaneous Determination of Sinensetin, Eupatorin, and 30-hydroxy-5,6,7,4'-tetramethoxyflavone in Orthosiphon stamineus Extracts

Mun Fei Yam,Elsnoussi Ali Hussin Mohamed,Lee Fung Ang,Li Pei,Yusrida Darwis,Roziahanim Mahmud,Mohd. Zaini Asmawi,Rusliza Basir,Mariam Ahmad,유혜현,김동현,정혜진 사단법인약침학회 2012 Journal of Acupuncture & Meridian Studies Vol.5 No.4

Orthosiphon stamineus extracts contain three flavonoids (3’-hydroxy-5, 6, 7, 4’-tetramethoxyflavone, sinensetin, and eupatorin) as bioactive substances. Previous reported high performance liquid chromatography- ultraviolet (HPLC-UV) methods for the determination of these flavonoids have several disadvantages, including unsatisfactory separation times and not being well validated according to International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) standard guidelines. A rapid, specific reversed-phase HPLC method with isocratic elution of acetonitrile: isopropyl alcohol: 20 mM phosphate buffer (NaH2-PO4) (30:15:55, v/v) (pH 3.5) at a flow-rate of 1 ml/minute, a column temperature of 25_C, and ultraviolet (UV) detection at 340 nm was developed. The method was validated and applied for quantification of different types of O stamineus extracts and fractions. The method allowed simultaneous determination of 3’-hydroxy-5,6,7,4’- tetramethoxyflavone, sinensetin, and eupatorin in the concentration range of 0.03052 e250 mg/ml. The limits of detection and quantification, respectively, were 0.0076 and 0.061 mg/ml for 3’-hydroxy-5,6,7,4’-tetramethoxyflavone, 0.0153 and 0.122 mg/ml for sinensetin and 0.0305 and 0.122 mg/ml for eupatorin. The percent relative standard deviation (% RSD) values for intraday were 0.048e0.368, 0.025e0.135, and 0.05e0.476 for 3’-hydroxy-5,6,7,4’-tetramethoxyflavone, sinensetin, and eupatorin, respectively, and those for intraday precision were 0.333e1.688, 0.722e1.055, and 0.548e1.819, respectively. The accuracy for intraday were 91.25%e103.38%, 94.32%e109.56%, and 92.85%e109.70% for 30-hydroxy-5,6,7,40-tetramethoxyflavone, sinensetin, and eupatorin, respectively, and those for interday accuracy were 97.49%e103.92%, 103.58% e104.57%, and 103.9%e105.33%, respectively. The method was found to be simple, accurate and precise and is recommended for routine quality control analysis of O stamineus extract containing the three flavonoids as the principle components in the extract.

Liver functions in combined models of the gentamicin induced nephrotoxicity and metabolic syndrome induced by high fat or fructose diets: a comparative study

Ibraheem Zaid O.,Farhan Sinan Subhi,Al Sumaidaee Ajwad,Al sufi Layth,Bashir Anas,Balwa Anmar,Basir Rusliza 한국독성학회 2021 Toxicological Research Vol.37 No.2

Metabolic syndrome is one of the major risk factors that lead to various serious complications like cardiovascular abnormalities, hyperlipidemia and diabetes. Its co-incidence with other organs dysfunction results in further deterioration of the condition or precipitation of other dysfunctions. This study aimed at studying the changes in the hepatic functions after the co-incidence of the high fat or fructose diets induced metabolic syndrome along with the gentamicin induced nephrotoxicity. Briefly, six groups of male Sprague Daley rats (n = 10–12) were fed with different feeding protocols; viz; standard rodent’s chow, an experimental high fat or high fructose diets feedings. For each, two groups were allocated that one of them was injected with normal saline and the other with 80 mg/kg/day I.P gentamicin during the last 24 days of the feeding period. The rats were monitored for changes in the metabolic data, glycemic control, lipid profile, renal and hepatic functions, oxidative stress and the inflammatory response. The study revealed stronger hepatic changes in the renal failure groups fed with the high fat diet rather than that in the groups fed with the high fructose diet. Although, the latter experienced a stronger deterioration in the glycemic control. The study suggests that the incidence of the hepatic changes is more linked to the incidence of the deterioration in the lipids profile that was observed after the high fat diet feeding. Overall, the co-incidence of the high fat diet induced metabolic syndrome along with the renal failure constitutes a risk factor for the hepatic dysfunction.

Orthosiphon stamineus Leaf Extract Protects Against Ethanol-Induced Gastropathy in Rats

Mun Fei Yam,Lee Fung Ang,Ibrahim Muhammad Salman,Omar Ziad Ameer,Vuanghao Lim,Lai Man Ong,Mariam Ahmad,Mohd. Zaini Asmawil,Rusliza Basir 한국식품영양과학회 2009 Journal of medicinal food Vol.12 No.5

Orthosiphon stamineus Benth., which is used as a gastroprotective herbal remedy in Malaysia, was assessed for its anti-ulcerogenic activity against ethanol-induced ulcers in rats. Fifty percent methanol was used to extract the oven-dried O. stamineus leaves. The extract was then lyophilized with a rotary evaporator and freeze-dried. Oral administration of O. stamineus methanolic extract (OSME) (125, 250, 500, and 1,000mg/kg) was found to significantly decrease the ulcer index (P<.01, P<.001, P<.001, and P<.001, respectively). Histological study of a section of the rat stomach also showed a marked improvement in the gastric mucosal damage in groups receiving OSME. In order to further investigate the gastroprotective mechanism of OSME, mucus secretion and lipid peroxidation level were estimated in vitro and ex vivo. OSME exhibited dose-dependent stimulation of mucus secretion (r=0.718, P<.001) and inhibition of lipid peroxidation in rat gastric mucosal homogenates (both in vitro [r=0.819, P<.05] and ex vivo [r=0.981, P<.05]). It was concluded that the gastroprotective mechanism of OSME was partly due to its ability to inhibit lipid peroxidation and stimulate gastric mucus secretion.