title: Anti-inflammatory potency of nano-formulated puerarin and curcumin in rats subjected to the lipopolysaccharide-induced inflammation.
abstract: Puerarin (PU) and curcumin (CU), used commonly in traditional Chinese medicine and Ayurveda, have been shown to possess potent anti-inflammatory, anti-oxidation, and neuro-protective properties. Despite the experimental success of CU and PU in in vitro and animal models, their effectiveness has not yet been demonstrated in clinical trials, possibly because of their poor bioavailability. We hypothesized that gold nanoparticle (AuNP)-formulated PU (PU-AuNP), CU (CU-AuNP), or a combination of PU and CU (PU-CU-AuNP) were a more effective and nontoxic alternative to their bulk (nonformulated) counterparts. To test the hypothesis, bioavailability, therapeutic potency, and toxicity of bulk CU and/or PU were compared with those of their nanotized counterparts in rats subjected to the lipopolysaccharide (LPS)-induced inflammation. This study showed that a 20-mg/kg dose of bulk PU or a mixture of PU and CU did not, while their nanotized counterparts, PU-AuNP, CU-AuNP, or PU-CU-AuNP, effectively suppressed the LPS-induced inflammation and cytotoxicity in rats. In addition, PU-CU-AuNP was more potent than PU-AuNP or CU-AuNP alone. The blank AuNP (bAuNP) at ≤40 mg/kg dose did not cause any adverse effects (blood and brain lactic acid concentrations, kidney function, and neuronal apoptosis were measured) in animals. Therefore, the present observations suggest that a bi-functional AuNP loaded with CU and PU may effectively suppress the LPS-induced inflammation and cytotoxicity provided the following conditions are met: (1) The AuNP dose is at or below the no-effect dose; (2) the nanoparticles release a therapeutic dose of CU and PU in vivo; and (3) the active ingredients are released into the intracellular component of the brain.
authors.affiliation: Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota , St. Paul, Minnesota.
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Singh
authors.forename: Yin
authors.initials: Y
authors.lastname: Jiang
authors.forename: Shveta
authors.initials: S
authors.lastname: Gupta
authors.forename: Mohamod
authors.initials: M
authors.lastname: Younus
authors.forename: Mohamod
authors.initials: M
authors.lastname: Ramzan
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry; D017209:Apoptosis / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology / Q000503:physiopathology; D007529:Isoflavones / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry; D008070:Lipopolysaccharides / Q000009:adverse effects; D008297:Male; D053758:Nanoparticles / Q000009:adverse effects / Q000737:chemistry; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D010936:Plant Extracts / Q000008:administration & dosage*; D029908:Pueraria / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000893:Anti-Inflammatory Agents; D007529:Isoflavones; D008070:Lipopolysaccharides; D010936:Plant Extracts; D003474:Curcumin; C033607:puerarin