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
2 major pharmaceutical targets:
• Inhibition of xanthine oxidase: e.g. allopurinol, febuxostat
• Increase renal uric acid excretion: e.g. probenecid
Pathogenesis
Endogenous source:
cellular break down
nucleic acids
Purines:
Hypoxanthine
Xanthine
oxidase
Guanine
Guanine deaminase
Xanthine
Xanthine
oxidase
Food rich in
purine
Uricase:
Non primates
Uric acid
Allantoin
Gastro-intestinal
elimination
33%
Renal
elimination
66%
Joint:
Monosodium
urate crystals
Inflammation
Gout
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
Natural gout prevention program
Normalize urate level
Uricosuric agent and
xanthase oxidase
inhibitors
GI tract health
Probiotic
Maintain joint health
DMOADs
DHA and EPA
Plant anti-inflammatory
Inflammation targets during gout flare
Neutrophil
migration
Cytokines
O2
Complement
Monocytes
-
DHA + EPA
Resident macrophages
Dendritic cells
..........
.
Resolvins
Protectins
Maresins
Apoptosis
Apolipoproteins
Noninflammatory
monosodium urate
crystals
Endothelium
Synovium
Enzymes
Inflammatory
monosodium
urate crystals
Blood
vessel
TGFβ
Clean up
by macrophages
Resident
macrophages
Resolution of inflammation
Goals during flares for natural antiinflammatory
• 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