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Absorption of andrographolides from Andrographis paniculata and its effect on CCl(4)-induced oxidative stress in rats

Akowuah GA, Zhari I, Mariam A, Yam MF

Food Chem Toxicol, 2009 Sep;47(9):2321-6.
PMID: 19540299 DOI: 10.1016/j.fct.2009.06.022

A simple and validated high-performance liquid chromatography (HPLC) method with UV detection has been used to determine the content of andrographolide (AP) and 14-deoxy-11,12-didehydroandrographolide (DIAP) in rat plasma after oral dose of methanol extract (1 g/kg body weight) of Andrographis paniculata leaf. An increase in plasma concentration of AP and DIAP was observed from 30 min to 3 h after oral administration of the extract. The maximum plasma concentrations of AP and DIAP were 1.42+/-0.09 microg/ml and 1.31+/-0.04 microg/ml, respectively. Fourteen days oral treatment of rats with the methanol extract (1 g/kg body weight) followed by CCl(4) administration preserved catalase (CAT), and superoxide dismutase (SOD) activities in erythrocytes, whereas plasma lipid peroxidation, alanine transaminase (ALT) and aspartate transaminase (AST) activities were restored to values comparable with control values. Treatment of rats with CCl(4) did not showed significant alteration (p>0.05) in plasma total antioxidant status (TAS) as compare to values of control group.
Anti-inflammatory and analgesic effects of ketoprofen in palm oil esters nanoemulsion

Sakeena MH, Yam MF, Elrashid SM, Munavvar AS, Azmin MN

J Oleo Sci, 2010;59(12):667-71.
PMID: 21099145

Ketoprofen is a potent non-steroidal anti-inflammatory drug has been used in the treatment of various kinds of pains, inflammation and arthritis. However, oral administration of ketoprofen produces serious gastrointestinal adverse effects. One of the promising methods to overcome these adverse effects is to administer the drug through the skin. The aim of the present work is to evaluate the anti-inflammatory and analgesic effects from topically applied ketoprofen entrapped palm oil esters (POEs) based nanoemulsion and to compare with market ketoprofen product, Fastum(®) gel. The novelty of this study is, use of POEs for the oil phase of nanoemulsion. The anti-inflammatory and analgesic studies were performed on rats by carrageenan-induced rat hind paw edema test and carrageenan-induced hyperalgesia pain threshold test to compare the ketoprofen entrapped POEs based nanoemulsion formulation and market formulation. Results indicated that there are no significant different between ketoprofen entrapped POEs nanoemulsion and market formulation in carrageenan-induced rat hind paw edema study and carrageenan-induced hyperalgesia pain threshold study. However, it shows a significant different between POEs nanoemulsion formulation and control group in these studies at p<0.05. From these results it was concluded that the developed nanoemulsion have great potential for topical application of ketoprofen.
Evaluation of the anti-pyretic potential of Orthosiphon stamineus Benth standardized extract

Yam MF, Ang LF, Basir R, Salman IM, Ameer OZ, Asmawi MZ

Inflammopharmacology, 2009 Feb;17(1):50-4.
PMID: 19127348 DOI: 10.1007/s10787-008-8038-3

The anti-pyretic activity of a standardized methanol/water (50/50) extract of Orthosiphon stamineus Benth. (SEOS) was investigated for its effect on normal body temperature and yeast-induced pyrexia in Sprague Dawley (SD) rats. The SEOS showed no effect on normal body temperature. Doses of 500 and 1000 mg/kg body weight of SEOS significantly reduced the yeast-induced elevation in body temperature. This effect persisted up to 4 h following the administration of the extract. The anti-pyretic effect of SEOS was comparable with that of paracetamol (acetaminophen in U.S) (150 mg/kg p.o.), a standard anti-pyretic agent. HPLC study revealed that rosmarinic acid, sinensetin, eupatorin and tetramethoxyflavone were present in SEOS in the amounts of 7.58%, 0.2%, 0.34% and 0.24% respectively. The LD(50) of the extract in rats was higher than 5000 mg/kg body weight. Therefore, the present study ascertained that SEOS possesses a significant anti-pyretic activity.
Fulltext Andrographolide effect on both Plasmodium falciparum infected and non infected RBCs membranes

Zaid OI, Abd Majid R, Sabariah MN, Hasidah MS, Al-Zihiry K, Yam MF, et al.

Asian Pac J Trop Med, 2015 Jul;8(7):507-12.
PMID: 26276279 DOI: 10.1016/j.apjtm.2015.06.007

OBJECTIVE: To explore whether its antiplasmodium effect of andrographolide is attributed to its plausible effect on the plasma membrane of both Plasmodium falciparum infected and non-infected RBCs.
METHODS: Anti-plasmodium effect of andrographolide against Plasmodium falciparum strains was screened using the conventional malaria drug sensitivity assay. The drug was incubated with uninfected RBCs to monitor its effect on their morphology, integrity and osmotic fragility. It was incubated with the plasmodium infected RBCs to monitor its effect on the parasite induced permeation pathways. Its effect on the potential of merozoites to invade new RBCs was tested using merozoite invasion assay.
RESULTS: It showed that at andrographolide was innocuous to RBCs at concentrations approach its therapeutic level against plasmodia. Nevertheless, this inertness was dwindled at higher concentrations.
CONCLUSIONS: In spite of its success to inhibit plasmodium induced permeation pathway and the potential of merozoites to invade new RBCs, its anti-plasmodium effect can't be attributed to these functions as they were attained at concentrations higher than what is required to eradicate the parasite. Consequently, other mechanisms may be associated with its claimed actions.
Cardiovascular activity of the n-butanol fraction of the methanol extract of Loranthus ferrugineus Roxb

Ameer OZ, Salman IM, Siddiqui MJ, Yam MF, Sriramaneni RN, Sadikun A, et al.

Braz. J. Med. Biol. Res., 2010 Feb;43(2):186-94.
PMID: 20084331

We investigated the vascular responses and the blood pressure reducing effects of different fractions obtained from the methanol extract of Loranthus ferrugineus Roxb. (F. Loranthaceae). By means of solvent-solvent extraction, L. ferrugineus methanol extract (LFME) was successively fractionated with chloroform, ethyl acetate and n-butanol. The ability of these LFME fractions to relax vascular smooth muscle against phenylephrine (PE)- and KCl-induced contractions in isolated rat aortic rings was determined. In another set of experiments, LFME fractions were tested for blood pressure lowering activity in anesthetized adult male Sprague-Dawley rats (250-300 g, 14-18 weeks). The n-butanol fraction of LFME (NBF-LFME) produced a significant concentration-dependent inhibition of PE- and KCl-induced aortic ring contractions compared to other fractions. Moreover, NBF-LFME had a significantly higher relaxant effect against PE- than against high K+-induced contractions. In anesthetized Sprague-Dawley rats, NBF-LFME significantly lowered blood pressure in a dose-dependent manner and with a relatively longer duration of action compared to the other fractions. HPLC, UV and IR spectra suggested the presence of terpenoid constituents in both LFME and NBF-LFME. Accordingly, we conclude that NBF-LFME is the most potent fraction producing a concentration-dependent relaxation in vascular smooth muscle in vitro and a dose-dependent blood pressure lowering activity in vivo. The cardiovascular effects of NBF-LFME are most likely attributable to its terpenoid content.
Plasmodium berghei ANKA Infection in ICR Mice as a Model of Cerebral Malaria

Basir R, Rahiman SF, Hasballah K, Chong W, Talib H, Yam M, et al.

Iran J Parasitol, 2012;7(4):62-74.
PMID: 23323093

Animal models with various combination of host-parasite have long been employed to study malaria pathogenesis. Here, we describe the combination of Plasmodium berghei ANKA infection in inbred ICR mice as a model of cerebral malaria (CM).
Role of norepinephrine & angiotensin II in the neural control of renal sodium & water handling in spontaneously hypertensive rats

Salman IM, Sattar MA, Ameer OZ, Abdullah NA, Yam MF, Salman HM, et al.

Indian J Med Res, 2010 Jun;131:786-92.
PMID: 20571167

A wealth of information concerning the essential role of renal sympathetic nerve activity (RSNA) in the regulation of renal function and mean arterial blood pressure homeostasis has been established. However, many important parameters with which RSNA interacts are yet to be explicitly characterized. Therefore, the present study aimed to investigate the impact of acute renal denervation (ARD) on sodium and water excretory responses to intravenous (iv) infusions of either norepinephrine (NE) or angiotensin II (Ang II) in anaesthetized spontaneously hypertensive rats (SHR).
Fulltext Interleukin-27 exhibited anti-inflammatory activity during Plasmodium berghei infection in mice

Fazalul Rahiman SS, Basir R, Talib H, Tie TH, Chuah YK, Jabbarzare M, et al.

Trop Biomed, 2013 Dec;30(4):663-80.
PMID: 24522137 MyJurnal

Interleukin-27 (IL-27) has a pleiotropic role either as a pro-inflammatory or anti-inflammatory cytokine in inflammatory related diseases. The role and involvement of IL-27 during malaria was investigated and the effects of modulating its release on the production of major inflammatory cytokines and the histopathological consequences in major affected organs during the infection were evaluated. Results showed that IL-27 concentration was significantly elevated throughout the infection but no positive correlation with the parasitaemia development observed. Augmentation of IL-27 significantly elevated the release of anti-inflammatory cytokine, IL-10 whereas antagonising and neutralising IL-27 produced the opposite. A significant elevation of pro-inflammatory cytokines (IFN-γ and IL-6) was also observed, both during augmentation and inhibition of IL-27. Thus, it is suggested that IL-27 exerts an anti-inflammatory activity in the Th1 type response by signalling the production of IL-10 during malaria. Histopathological examination showed sequestration of PRBC in the microvasculature of major organs in malarial mice. Other significant histopathological changes include hyperplasia and hypertrophy of the Kupffer cells in the liver, hyaline membrane formation in lung tissue, enlargement of the white and red pulp followed by the disappearance of germinal centre of the spleen, and tubular vacuolation of the kidney tissues. In conclusion, it is suggested that IL-27 may possibly acts as an anti-inflammatory cytokine during the infection. Modulation of its release produced a positive impact on inflammatory cytokine production during the infection, suggesting its potential in malaria immunotherapy, in which the host may benefit from its inhibition.
Fulltext Modulation of interleukin-18 release produced positive outcomes on parasitaemia development and cytokines production during malaria in mice

Basir R, Hasballah K, Jabbarzare M, Gam LH, Abdul Majid AM, Yam MF, et al.

Trop Biomed, 2012 Sep;29(3):405-21.
PMID: 23018504 MyJurnal

The involvement of interleukin-18 (IL-18) and the effects of modulating its release on the course of malaria infection were investigated using Plasmodium berghei ANKA infection in ICR mice as a model. Results demonstrated that plasma IL-18 concentrations in malarial mice were significantly elevated and positively correlated with the percentage parasitaemia development. Significant expressions of IL-18 were also observed in the brain, spleen and liver tissues. Slower development of parasitaemia was observed significantly upon inhibition and neutralization of IL-18, whereas faster development of parasitaemia was recorded when the circulating levels of IL-18 were further augmented during the infection. Inhibition and neutralization of IL-18 production also resulted in a significant decrease of plasma concentrations of pro-inflammatory cytokines (TNFα, IFNγ, IL-1α and IL-6), whereas the anti-inflammatory cytokine, IL-10, was significantly increased. Augmenting the release of IL- 18 during the infection on the other hand resulted in the opposite. Early mortality in malarial mice was also observed when the circulating levels of IL-18 were further augmented. Results proved the important role of IL-18 in immune response against malaria and suggest that IL-8 is pro-inflammatory in nature and may involve in mediating the severity of the infection through a pathway of elevating the pro-inflammatory cytokine and limiting the release of anti-inflammatory cytokine.