J Nutr. 2005 Sep;135(9):2096-102.
Punica granatum L. extract (Pomegranate) inhibits IL-1beta-induced expression of matrix metalloproteinases by inhibiting the activation of MAP kinases and NF-kappaB in human chondrocytes in vitro.
Ahmed S, Wang N, Hafeez BB, Cheruvu VK, Haqqi TM.
Division of Rheumatic Diseases, Department of Medicine, Case Western University, Cleveland, OH 44106, USA.
Interleukin (IL)-1beta induces the expression of matrix metalloproteinases (MMPs) implicated in cartilage resorption and joint degradation in osteoarthritis (OA). Pomegranate fruit extract (PFE) was recently shown to exert anti-inflammatory effects in different disease models. However, no studies have been undertaken to investigate whether PFE constituents protect articular cartilage. In the present studies, OA chondrocytes or cartilage explants were pretreated with PFE and then stimulated with IL-1beta at different time points in vitro. The amounts of proteoglycan released were measured by a colorimetric assay. The expression of MMPs, phosphorylation of the inhibitor of kappaBalpha (IkappaBalpha) and mitogen-activated protein kinases (MAPKs) was determined by Western immunoblotting. Expression of mRNA was quantified by real-time PCR. MAPK enzyme activity was assayed by in vitro kinase assay. Activation of nuclear factor-kappaB (NF-kappaB) was determined by electrophoretic mobility shift assay. PFE inhibited the IL-1beta-induced proteoglycan breakdown in cartilage explants in vitro. At the cellular level, PFE (6.25-25 mg/L) inhibited the IL-1beta-induced expression of MMP-1, -3, and -13 protein in the medium (P < 0.05) and this was associated with the inhibition of mRNA expression. IL-1beta-induced phosphorylation of p38-MAPK, but not that of c-Jun-N-terminal kinase or extracellular regulated kinase, was most susceptible to inhibition by low doses of PFE, and the addition of PFE blocked the activity of p38-MAPK in a kinase activity assay. PFE also inhibited the IL-1beta-induced phosphorylation of IkappaBalpha and the DNA binding activity of the transcription factor NF-kappaB in OA chondrocytes. Taken together, these novel results indicate that PFE or compounds derived from it may inhibit cartilage degradation in OA and may also be a useful nutritive supplement for maintaining joint integrity and function.
Aslam MN, Lansky EP, Varani J. Department of Pathology, The University of Michigan Medical School, 1301 Catherine Road/Box 0602, Ann Arbor, MI 48109, USA.
Pomegranate (Punica granatum) is an ancient fruit with exceptionally rich ethnomedical applications. The peel (pericarp) is well regarded for its astringent properties; the seeds for conferring invulnerability in combat and stimulating beauty and fertility. Here, aqueous fractions prepared from the fruit’s peel and fermented juice and lipophilic fractions prepared from pomegranate seeds were examined for effects on human epidermal keratinocyte and human dermal fibroblast function. Pomegranate seed oil, but not aqueous extracts of fermented juice, peel or seed cake, was shown to stimulate keratinocyte proliferation in monolayer culture. In parallel, a mild thickening of the epidermis (without the loss of ordered differentiation) was observed in skin organ culture. The same pomegranate seed oil that stimulated keratinocyte proliferation was without effect on fibroblast function. In contrast, pomegranate peel extract (and to a lesser extent, both the fermented juice and seed cake extracts) stimulated type I procollagen synthesis and inhibited matrix metalloproteinase-1 (MMP-1; interstitial collagenase) production by dermal fibroblasts, but had no growth-supporting effect on keratinocytes. These results suggest heuristic potential of pomegranate fractions for facilitating skin repair in a polar manner, namely aqueous extracts (especially of pomegranate peel) promoting regeneration of dermis, and pomegranate seed oil promoting regeneration of epidermis.