Gout • Elevation of serum uric acid level: hyperuricemia

primary risk factor ,predisposes to gout > 6.8mg/dl

• Deposition of uric acid crystals (monosodium urate) in the joint

• Acute inflammatory arthritis• Management of the disease– Between flares

• Normalize urate level: goal below 6 mg/dl• Maintain health joint

– During flares: control and resolution of inflammation

Endogenous source:cellular break down

nucleic acids

Food rich in purine

Purines: Hypoxanthine Guanine

Xanthine

Uric acid

Allantoin

Gastro-intestinal elimination

33%

Renal elimination

66%

Joint:Monosodiumurate crystalsInflammation

Gout

Uricase: Non primates

Xanthine oxidase

Xanthine oxidase

Guanine deaminase

2 major pharmaceutical targets:• Inhibition of xanthine oxidase: e.g. allopurinol, febuxostat• Increase renal uric acid excretion: e.g. probenecid

Pathogenesis

Normalize urate level• Gastro-intestinal tract: probiotics• Inhibition of xanthine oxidase

– Methanol extract of Chrysanthemum sinense (china)– Methanol extract of Larix laricinia ( North America)– Methanol extract of Coccinia grandis (India)– Methanol extract of Vitex negundo (India)– Chloroform extract of Erythrina stricta (India, China, Vietnam, Thailand)– Various plant extracts containing rutin and quercetin (Biota orientalis and

others)– Cassia oil from Cinnamomum cassia

• Increase renal uric acid excretion:– Methanol extract of Orthosiphon stamineus– Lignans from Phyllanthus niruri ( Southeast Asia and Latin America)

• Mixed: (XOI and renal): Paedaria scandens ( China)

Maintain joint health

• DMOADs: glucosamine, chondroitin, insaponifiable fraction of soja and avocado

• Promotion of resolution of inflammation: DHA and EPA

• Plant derived anti-inflammatory agents– Curcuma– Meadowsweet– Black current

Normalize urate levelUricosuric agent and

xanthase oxidase inhibitors

GI tract health Probiotic

Maintain joint healthDMOADsDHA and EPAPlant anti-inflammatory

Natural gout prevention program

Inflammation targets during gout flareBlood vessel

Endothelium

Synovium

Resident macrophagesDendritic cells

O2-

Enzymes

ComplementCytokines

. ...

. . .......Apolipoproteins

Clean up by macrophages

Neutrophil migration

Apoptosis

TGFβ

Monocytes

Resident macrophages

Inflammatorymonosodiumurate crystals

Noninflammatory monosodium urate

crystals

ResolvinsProtectinsMaresins

DHA + EPA

Resolution of inflammation

Goals during flares for natural anti-inflammatory

• Inhibition of cytokine production: IL-1β , IL -6, IL-8 and TNF-α

• Neutralize oxygen radicals and enzymes produced by activated macrophages

• Promotes TGF β production• Promote resolution of inflammation