Browsing by Author "Mukhtar, H."
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Item Chitosan-based nanoformulated (–)-epigallocatechin-3-gallate (EGCG) modulates human keratinocyte-induced responses and alleviates imiquimod-induced murine psoriasiform dermatitis(Taylor & Francis, 2018) Chamcheu, J.C.; Siddiqui, I.A.; Adhami, V.M.; Esnault, S.; Bharali, D.J.; Babatunde, A.S.; Adame, S.; Massey, R.J.; Wood, G.S.; Longley, B.J.; Mousa, S.A., Mukhtar, H.; Mousa, S.A.,; Mukhtar, H.Background: Psoriasis is a chronic and currently incurable inflammatory skin disease characterized by hyperproliferation, aberrant differentiation, and inflammation, leading to disrupted skin barrier function. The use of natural agents that can abrogate these effects could be useful for the treatment of psoriasis. Earlier studies have shown that treatment of keratinocytes and mouse skin with the green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) mitigated inflammation and increased the expression of caspase-14 while promoting epidermal differentiation and cornification. However, bioavailability issues have restricted the development of EGCG for the treatment of psoriasis. Materials and methods: To overcome these limitations, we employed a chitosan-based polymeric nanoparticle formulation of EGCG (CHI-EGCG-NPs, hereafter termed nanoEGCG) suitable for topical delivery for treating psoriasis. We investigated and compared the efficacy of nanoEGCG versus native or free EGCG in vitro and in an in vivo imiquimod (IMQ)-induced murine psoriasis-like dermatitis model. The in vivo relevance and efficacy of nanoEGCG formulation (48 μg/mouse) were assessed in an IMQ-induced mouse psoriasis-like skin lesion model compared to free EGCG (1 mg/mouse). Results: Like free EGCG, nanoEGCG treatment induced differentiation, and decreased proliferation and inflammatory responses in cultured keratinocytes, but with a 4-fold dose advantage. Topically applied nanoEGCG elicited a significant (p,0.01) amelioration of psoriasiform pathological markers in IMQ-induced mouse skin lesions, including reductions in ear and skin thickness, erythema and scales, proliferation (Ki-67), infiltratory immune cells (mast cells, neutrophils, macrophages, and CD4+ T cells), and angiogenesis (CD31). We also observed increases in the protein expression of caspase-14, early (keratin-10) and late (filaggrin and loricrin) markers of differentiation, and the activator protein-1 factor (JunB). Importantly, a significant modulation of several psoriasis-related inflammatory cytokines and chemokines was observed compared to the high dose of free EGCG (p,0.05). Taken together, topically applied nanoEGCG displayed a .20-fold dose advantage over free EGCG. Conclusion: Based on these observations, our nanoEGCG formulation represents a promising drug-delivery strategy for treating psoriasis and possibly other inflammatory skin diseases. Keywords: chitosan nanoparticles, topical delivery of chitosan nanoformulated EGCG, psoriasis-like skin inflammation, phytochemical treatment of psoriasis, normal human epidermal keratinocytes, differentiation, anti-inflammatory actionItem Comparative Antileukemic Activity of a Tetranorditerpene Isolated from Polyalthia longifolia Leaves and the Derivative against Human Leukemia HL-60 cells(Japan Oil Chemists’ Society., 2017) Afolabi, S.; Olorundare, O.; Ninomiya, M.; Babatunde, A.; Mukhtar, H.; Koketsu, M.Abstract: The discovery of potent cytotoxic isolates from botanicals provides an opportunity to explore this viable tool for cancer chemoprevention. The antileukemic potential of clerodane diterpene from Polyalthia longifolia leaves has already been established. However, in this present study, utilizing chromatographic techniques we report for the first time, the isolation of a rare tetranorditerpene (compound 1) from P. longifolia. The structure of compound 1 was elucidated and confirmed by spectrophotometric data. UPLCMS analysis was conducted on the methanolic extract, ethyl acetate fraction, and isolated tetranorditerpene showed that the tetranorditerpene is one of the major constituents of the plant with a retention time of 30.78 min. In addition, a methyl ester derivative (compound 2) of the isolated tetranorditerpene was synthesized. Using the CCK-8 assay, we compared the cytotoxic potential of isolated tetranorditerpene (1) and methyl ester derivative (2) with the previously isolated clerodane diterpenes. Our results showed that the methyl ester derivative (2) displayed the highest inhibitory activity against human leukemia HL-60 cells. The isolated tetranorditerpene (1) did not exhibit significant inhibitory effect against HL-60 cells. Morphological examination indicated chromatin condensation and nuclear fragmentation suggesting induction of apoptosis in compound 2 treated HL-60 cells. The methyl esterification of the isolated tetranorditerpene (1) conferred on it a significant level of antileukemic activity suggesting the possibility of a synergistic relationship between pure compound isolation and synthetic reaction in the discovery of new chemopreventive agents.