The leaves of Carica papaya (CP) are rich in natural antioxidants. Carica papaya has traditionally been used to treat various ailments, including skin diseases. This study aims to decipher the antioxidant effects and phytochemical content of different CP leaf extracts (CPEs) obtained using supercritical carbon dioxide (scCO2) and conventional extraction methods. The antioxidant activities of CPEs were evaluated by cell-free (1,1-diphenyl-2-picryl-hydrazyl (DPPH) and ferric-reduced antioxidative power (FRAP)) and cell-based (H2O2) assay. Both C. papaya leaf scCO2 extract with 5% ethanol (CPSCE) and C. papaya leaf scCO2 extract (CPSC) exhibited stronger DPPH radical scavenging activity than conventional extracts. In the FRAP assay, two hydrophilic extracts (C. papaya leaf ethanol extract (CPEE) and C. papaya freeze-dried leaf juice (CPFD)) showed relatively stronger reducing power compared to lipophilic extracts. Cell-based assays showed that CPFD significantly protected skin fibroblasts from H2O2-induced oxidative stress in both pre-and post-treatment. CPEE protected skin fibroblasts from oxidative stress in a dose-dependent manner while CPSCE significantly triggered the fibroblast recovery after treatment with H2O2. GC-MS analysis indicated that CPSCE had the highest α-tocopherol and squalene contents. By contrast, both CP hydrophilic extracts (CPEE and CPFD) had a higher total phenolic content (TPC) and rutin content than the lipophilic extracts. Overall, CPEs extracted using green and conventional extraction methods showed antioxidative potential in both cell-based and cell-free assays due to their lipophilic and hydrophilic antioxidants, respectively.
Hydrogels are an attractive platform for drug delivery to the skin. Current cellulose hydrogel developments commonly focus on readily available bleached woody cellulose. Considering the detrimental environmental impacts of bleaching reagents, unbleached non-woody biomass was proposed as an alternative. Herein, this study aims to develop hydrogel from native cellulose extracted from oil palm empty fruit bunches for dermal drug delivery with an emphasis on evaluating the effect of alkali solvent compositions on hydrogel formation. Unbleached dissolving pulps were solubilized in alkali solvents containing sodium hydroxide (NaOH) (6-8%w/v) and urea (4-6%w/v) before crosslinking. Hydrogels were loaded with ibuprofen for skin permeation studies. Light brownish hydrogels formed are aesthetically acceptable and biodegradable with low cytotoxicity. NaOH content has a dominant role over urea where thinner and deformable crosslinked network walls in a porous hydrogel structure are associated with high NaOH content. Synergistic effects (cellulose solubility: 94 %; swelling ratio: ~2800 %) were observed at 7%w/v NaOH and 4%w/v urea with low toxicity. Most hydrogels showed >80 % of ibuprofen permeated into the skin and this increased with the swelling ratio of hydrogels. Unbleached cellulose pulps have excellent potential for hydrogel fabrication with outstanding physicomechanical properties for dermal drug delivery.
Sulfuretin, a naturally occurring aurone is reported to inhibit macrophage and microglia activation. A series of aurones incorporating basic amines and lipophilic functionalities at ring A and/or ring B were synthesized to improve upon present sulfuretin activity towards targeting brain microglia while overcoming the blood-brain barrier (BBB). Evaluation of the ability of the aurones to inhibit lipopolysaccharide (LPS)-stimulated nitric oxide (NO) secretion by murine BV-2 microglia has identified several inhibitors showing significant NO reduction at 1 to 10 µM. Potent inhibitors were represented by aurones with bulky, planar moieties at ring A (3f) or at ring B (1e and 1f) and having a pendant piperidine at ring B (1a, 2a, 2b, and 3f). The active aurones inhibited the BV-2 microglia polarizing towards the M1 state as indicated by attenuation of IL-1β and TNF-α secretions in LPS-activated microglia but did not induce the microglia towards the M2 state. The aurones 2a, 2b, and 1f showed high passive BBB permeability in the parallel artificial membrane permeability assay (PAMPA) owing to their optimal lipophilicities. 2a, being non-cell toxic, BBB permeant and potent, represents a new lead for the development of aurones as inhibitors of activated microglia.
Benign prostate hyperplasia (BPH) is an enlargement of the prostate gland, because of hormonal changes in aging males which contribute significantly to excessive proliferation over apoptosis of prostatic cells. The anti-proliferative and induced apoptotic activities of Eurycoma longifolia quassinoids on cancer cell lines could be promising therapeutic targets on BPH. Hitherto, no report of the quassinoids against BPH problem was available. In this study, a systematic phytochemical fractionation of the root extract, TAF2 was performed, which led to the discovery of nine previously described C20 quassinoids (1-9). Two undescribed C20 (10 and 12) and one undescribed (11) C19 quassinoids were identified by detailed NMR and HR-ESI-MS data analysis. Their absolute configurations were assigned by ECD spectral analysis. The quassinoids (1-12) were tested for inhibitory activity against the proliferation of human BPH-1 and human skin Hs27 fibroblast cells cultured in vitro. 1, 2 and 3 at 10 μM significantly reduced BPH-1 cell viability and were cytotoxic to Hs27 fibroblast cells. 2 was selected for further study of anti-BPH activity against testosterone induced BPH rats. At 5 mg/kg, 2 reduced the rat prostatic weight and prostatic index, consistent with the decrease in papillary acini number and epithelial thickness of the prostate tissues. These quassinoids may be potential anti-BPH compounds that require further studies.