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Antihyperuricemic lignans from the leaves of Phyllanthus niruri

Murugaiyah V, Chan KL

Planta Med, 2006 Nov;72(14):1262-7.
PMID: 16953466 DOI: 10.1055/s-2006-947224

The methanol extract from the leaves of Phyllanthus niruri L. showed oral antihyperuricemic activity in potassium oxonate- and uric acid-induced hyperuricemic rats. Fractionation of the extract by resin chromatography led to the isolation of a less polar fraction which exhibited the highest reduction of plasma uric acid. Further antihyperuricemic-guided purification of the fraction afforded three lignans, phyllanthin (1), hypophyllanthin (2) and phyltetralin (3), of which 1 significantly reversed the plasma uric acid level of hyperuricemic animals to its normal level in a dose-dependent manner, comparable to that of allopurinol, benzbromarone and probenecid which are used clinically for the treatment of hyperuricemia and gout. Thus, the lignans of P. niruri are potential antihyperuricemic agents worthy of further investigation.

Matched MeSH terms: Uric Acid/blood*
Fulltext Antidiabetic, Antihyperlipidemic, Antioxidant, Anti-inflammatory Activities of Ethanolic Seed Extract of Annona reticulata L. in Streptozotocin Induced Diabetic Rats

Wen W, Lin Y, Ti Z

Front Endocrinol (Lausanne), 2019;10:716.
PMID: 31708869 DOI: 10.3389/fendo.2019.00716

Annona reticulata L. (Bullock's heart) is a pantropic tree commonly known as custard apple, which is used therapeutically for a variety of maladies. The present research was carried out to evaluate the possible protective effects of Annona reticulata L. (A. reticulata) ethanolic seed extract on an experimentally induced type 2 diabetes rat model. Male Albino Wistar rats were randomly divided into five groups with six animals in each group viz., control rats in group I, diabetic rats in group II, diabetic rats with 50 and 100 mg/kg/bw of ethanolic seed extract of A. reticulata in groups III and IV, respectively, and diabetic rats with metformin in group V. Treatment was given for 42 consecutive days through oral route by oro-gastric gavage. Administration of A. reticulata seed extract to diabetes rats significantly restored the alterations in the levels of body weight, food and water intake, fasting blood glucose (FBG), insulin levels, insulin sensitivity, HbA1c, HOMA-IR, islet area and insulin positive cells. Furthermore, A. reticulata significantly decreased the levels of triglycerides, cholesterol, LDL, and significantly increased the HDL in diabetic rats. A. reticulata effectively ameliorated the enzymatic (ALT, AST, ALP, GGT) and modification of histopathological changes in diabetic rats. The serum levels of the BUN, creatinine levels, uric acid, urine volume, and urinary protein were significantly declined with a significant elevation in CCr in diabetic rats treated with A. reticulata. MDA and NO levels were significantly reduced with an enhancement in SOD, CAT, and GPx antioxidant enzyme activities in the kidney, liver, and pancreas of diabetic rats treated with A. reticulata. Diabetic rats treated with A. reticulata have shown up-regulation in mRNA expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), NAD(P)H:quinone oxidoreductase 1 (NQO1), Heme oxygenase-1 (HO-1) and protein expression level of Nrf2 with diminution in Keap1 mRNA expression level in pancreas, kidney, and liver. From the outcome of the current results, it can be inferred that seed extract of A. reticulata exhibits a protective effect in diabetic rats through its anti-diabetic, anti-hyperlipidemic, antioxidant and anti-inflammatory effects and could be considered as a promising treatment therapy in the treatment of diabetes mellitus.

Matched MeSH terms: Uric Acid
Alterations of serum and saliva oxidative markers in patients with bronchial asthma

Abboud MM, Al-Rawashde FA, Al-Zayadneh EM

J Asthma, 2022 Nov;59(11):2154-2161.
PMID: 34855555 DOI: 10.1080/02770903.2021.2008426

BACKGROUNDS: The development of asthma is highly affected by exposure to exogenous and endogenous oxidative molecules, but the impact of this exposure on the pathophysiology of asthma has received little attention.
OBJECTIVES: Evaluating group of selective oxidative stress markers as a tool in the management of asthma disease.
METHODS: In comparison with matched healthy controls, levels of the oxidant and antioxidant markers: lipid peroxidation malondialdehyde (MDA), Total glutathione (tGSH), Uric acid (UA), Glutathione peroxidase (GPx), Catalase (CAT) superoxide dismutase (SOD), and Total antioxidant capacity (TAC) were assessed in serum and saliva of different asthma groups.
RESULTS: All oxidative markers in serum and saliva of asthma patients showed significant alterations from normal healthy controls (P 0.05).
CONCLUSION: Determination of the oxidative markers GPx, CAT, UA in serum or saliva can distinguish asthma from healthy states. The serum levels of UA and TAC are highly effective in monitoring asthma severity, while the salivary GPx, CAT, UA, MDA are beneficial in the management of childhood asthma. Discrimination of the age factor between asthma groups can be achieved by testing GPx, SOD, TAC in serum.

Matched MeSH terms: Uric Acid
A survey on the management of gout in Malaysia

Yeap SS, Goh EM, Gun SC

Int J Rheum Dis, 2009 Dec;12(4):329-35.
PMID: 20374371 DOI: 10.1111/j.1756-185X.2009.01431.x

AIM: The aim of this study was to ascertain the management of gout by doctors in Malaysia.
METHODS: A cross-sectional questionnaire survey was carried out among doctors attending rheumatology post-graduate courses, where gout was not a lecture topic.
RESULTS: A total of 128 questionnaires were analyzed, of which the majority (67: 52.3%) were general practitioners. In the treatment of acute gout, 68.0% use non-selective non-steroidal anti-inflammatory drugs (NSAIDs), 53.9% use selective COX-2 inhibitors (coxibs), 66.4% use colchicine and 10.2% use allopurinol (ALLO). In the treatment of chronic gout, 36.7% use NSAIDs, 44.5% use coxibs, 19.5% use colchicine and 93% use ALLO. In both acute and chronic gout, corticosteroids (CS) are not used by over 90% of respondents. Fifty percent would stop ALLO during an acute attack. 95.3% do not start ALLO during an acute attack; 87.5% would start ALLO after the attack, with a median of 14 days afterwards. Once ALLO was started, 54.7% would continue indefinitely. Regarding target urate levels while on treatment, 10.9% would be satisfied with a high normal range, 21.9% middle of the range, 18.0% low normal range and 45.3% anywhere within the normal range. Fifteen percent would treat asymptomatic hyperuricemia.
CONCLUSIONS: In Malaysia, anti-inflammatory agents are most commonly used for the treatment of acute and chronic gout, with corticosteroid usage at a low level. However, there are areas of concern regarding the diagnosis of gout and the usage of ALLO which are not consistent with current guidelines

Matched MeSH terms: Uric Acid/blood
A survey of the primary care management of osteoarthritis in Malaysia: A view from a rheumatologist's perspective

Arshad A, Rashid R, Das Gupta E

Int J Rheum Dis, 2008;11(3):246-250.
DOI: 10.1111/j.1756-185X.2008.00367.x

Objective: Primary care management of knee osteoarthritis (OA) has received little attention in the scientific literature and the main reason for this survey is to study and explore the variations and patterns of primary care management and assess both conventional and complementary therapy usage in knee OA in the primary care setting.
Methods: A cross-sectional survey of 200 randomly selected general practitioners (GPs) in the peninsular states of Malaysia was undertaken using a questionnaire. The GPs involved were asked about basic knowledge of OA in terms of diagnosis, investigation, and treatment. They were also asked about their usage of conventional and complementary medication.
Results: One hundred and eighty (90%) GPs responded to the questionnaires sent: 77% were in solo practice and 33% in group practice. Most of the GPs surveyed (60%) had been in practice for more than 10 years, 30% for 5-10 years and 10% were in practice for less than 5 years. Of GPs surveyed, 55% saw an average of more than 20 patients per week, 35% about 10-20 patients and 10% less than 10 patients per week. Of GPs surveyed, 65% would arrange an X-ray, 55% would arrange a blood test, mostly serum uric acid, rheumatoid factor and erythrocyte sedimentation rate. Pharmacological management consists of first-line treatment with non-steroidal anti-inflammatory drugs (NSAIDs) (61%), analgesics (35%) or a combination of the two (4%). Non-pharmacological management consisted of advice on exercise (27%), weight reduction (33%) and referral to physiotherapy (10%). Of GPs surveyed, 85% prescribed some form of complementary medications, 60% prescribed glucosamine sulphate, 21% chondroitin sulphate, 11% cod liver oil and 9% evening primrose oil. Only 10% of GPs surveyed perform intra-articular injections.
Conclusion: The data suggest that in the primary care setting, the majority of GPs over-investigate the diagnosis of OA. Pharmacological interventions largely concentrate on analgesics and NSAIDs. The use of physiotheraphy and non-drug approaches were significantly under-utilized. There is a need to further educate GPs in the management of OA.

Matched MeSH terms: Uric Acid
Fulltext A single-centre experience of febuxostat as a second-line urate-lowering therapy

Ong SG, Ding HJ

Malays Fam Physician, 2021 Mar 25;16(1):50-55.
PMID: 33948142 DOI: 10.51866/oa0892

Introduction: The purpose of this study was to describe the local experience in terms of drug efficacy and safety using a new xanthine oxidase inhibitor, febuxostat, as a second-line urate-lowering therapy (ULT) in gout patients with normal renal function and chronic kidney disease.
Methods: This cross-sectional study included all gout patients who attended the rheumatology clinic from January 2013 to June 2018 and had received febuxostat as a second-line ULT. Analysis focused on the proportion of gout patients who achieved target serum urate (sUA) of <360 μmol/L, duration taken to achieve target sUA, and febuxostat dosage at achievement of target sUA. Safety assessments included comparison of serum creatinine, estimated glomerular filtration rate (eGFR), and serum alanine aminotransferase (ALT) at baseline, at achievement of target sUA, and at 12-monthly intervals.
Results: Majority (90.9%) of patients achieved target sUA. Median duration required to achieve target sUA was 5.5 months with IQR (interquartile range) of 8.5. Five (22.7%) patients achieved target sUA within one month of therapy with febuxostat 40 mg per day. Eleven (55%) patients achieved target sUA within six months and 16 (80%) by 12 months. Equal proportion of patients achieved target sUA with febuxostat 40 mg per day and 80 mg per day, respectively. There was no significant difference in the changes in serum creatinine level, eGFR and ALT from baseline and at achievement of target sUA, nor at 12-monthly intervals throughout the duration of febuxostat therapy. Apart from three patients who developed hypersensitivity reactions to febuxostat, no other adverse events were reported.
Conclusion: A significant proportion of gout patients with CKD managed to achieve target sUA with a lower dose of febuxostat at 40 mg per day and it is reasonable to maintain this dose for up to six months before considering dose escalation.

Matched MeSH terms: Uric Acid
A simple and sensitive fluorescence based biosensor for the determination of uric acid using H2O2-sensitive quantum dots/dual enzymes

Azmi NE, Ramli NI, Abdullah J, Abdul Hamid MA, Sidek H, Abd Rahman S, et al.

Biosens Bioelectron, 2015 May 15;67:129-33.
PMID: 25113659 DOI: 10.1016/j.bios.2014.07.056

A novel optical detection system consisting of combination of uricase/HRP-CdS quantum dots (QDs) for the determination of uric acid in urine sample is described. The QDs was used as an indicator to reveal fluorescence property of the system resulting from enzymatic reaction of uricase and HRP (horseradish peroxidase), which is involved in oxidizing uric acid to allaintoin and hydrogen peroxide. The hydrogen peroxide produced was able to quench the QDs fluorescence, which was proportional to uric acid concentration. The system demonstrated sufficient activity of uricase and HRP at a ratio of 5U:5U and pH 7.0. The linearity of the system toward uric acid was in the concentration range of 125-1000 µM with detection limit of 125 µM.

Matched MeSH terms: Uric Acid/isolation & purification*; Uric Acid/urine; Uric Acid/chemistry
Fulltext A pilot study of the primary care management of knee osteoarthritis in the Northern States of Malaysia.

Arshad, A., Rashid, R.

International Medical Journal Malaysia, 2008;7(2):31-36.
MyJurnal

Introduction: Primary care management of knee osteoarthritis OA has received little attention in the scientific literature and the main reason of this survey is to study and explore the variations and patterns of primary care management and assess both conventional and complementary therapy usage in knee OA in the primary care setting. Materials and Methods: A cross sectional survey of 100 randomly selected general practitioners (GPs) in the northern states of Malaysia (Kedah, Perlis, Pulau Pinang) was undertaken using questionnaires. The GPs involved were asked about basic knowledge of OA in terms of diagnosis, investigation, and treatment of OA. They were also asked their usage of conventional and complementary medication. Results: 80 (80%) GPs responded to the questionnaires sent. 85% of GPs were in solo practice and 15% in group practice. Most of the GPs surveyed (69%) were in practice for more than 10 years, 21% in 5- 10 years and 10% were in practice for less than 5 years. 65% GPs surveyed see an average of more than 20 patients per week, 25% see about 10- 20 patients and 10% see less than 10 patients per week. 75% of GPs surveyed would arrange an X-ray. 65% of GPs surveyed will arrange a blood test, mostly serum uric acid, rheumatoid factor and ESR. Pharmacological management consists of first line treatment with analgesics (32%), NSAIDs (59%) or a combination of the two (4%). Non-pharmacological management consist of advise an exercise (37%), weight reduction (23%) and referral to physiotherapy (8%). 89% of GPs surveyed prescribed some form of complementary medications. 68% prescribed glucosamine sulphate, 29% chondroitin sulphate, 18% cod liver oil, 12% evening primrose oil. Only 5% of GPs surveyed perform intra- articular injection. Conclusion: The data suggest that in the primary care, majority of GP over investigate the diagnosis of OA. Pharmacological interventions largely concentrate on analgesic and NSAIDs. The use of physiotherapy and non drug approach were enormously under-utilized. There is a need to further educate GPs in the management of OA.

Matched MeSH terms: Uric Acid
A comparative study of relative incidence of stone types between a transient military population and the indigenous population of the Hawaiian Islands

Wurster JC, Ceccarelli FE, Chinn HY

J Urol, 1970 Oct;104(4):581-5.
PMID: 5476472
Matched MeSH terms: Uric Acid/analysis*; Uric Acid/blood