Papers by Lucia Dwi Antika
The Journal of Nutritional Biochemistry, 2017
Osteoporosis is one of the most prevalent forms of age-related bone diseases. Increased bone loss... more Osteoporosis is one of the most prevalent forms of age-related bone diseases. Increased bone loss with advancing age has become a grave public health concern. This study examined whether phlorizin and phloretin, dihydrochalcones in apple peels, inhibited senile osteoporosis through enhancing osteoblastogenic bone formation in cell-based and aged mouse models. Submicromolar phloretin and phlorizin markedly stimulated osteoblast differentiation of MC3T3-E1 cells with increased transcription of Runx2 and osteocalcin. Senescence accelerated mice-prone 6 (SAMP6) were orally supplemented with 10 mg/kg phlorizin and phloretin daily for 12 weeks. Male senescence-accelerate resistant mice-strain R1 (SAMR1) was employed as a nonosteoporotic age-matched control. Oral administration of ploretin and phorizin boosted bone mineralization in all the bones of femur, tibia and vertebra of SAMP6. In particular, phlorizin reduced serum RANKL/OPG ratio and diminished TRAP-positive osteoclasts in trabecular bones of SAMP6. Additionally, treating phlorizin to SAMP6 inhibited the osteoporotic resorption in distal femoral bones through up-regulating expression of BMP-2 and collagen-1 and decreasing production of matrix-degrading cathepsin K and MMP-9. Finally, phlorizin and phloretin antagonized GSK-3β induction and β-catenin phosphorylation in osteoblasts and aged mouse bones. Therefore, phlorizin and phloretin were potential therapeutic agents encumbering senile osteoporosis through promoting bone forming-osteoblastogenesis via modulation of GSK-3β/βcatenin-dependent signaling.
Mini-Reviews in Medicinal Chemistry
: Diabetes mellitus is the most common chronic metabolic disorder and is considered one of the le... more : Diabetes mellitus is the most common chronic metabolic disorder and is considered one of the leading causes of morbidity and mortality. The improperly-treated chronic hyperglycemia of diabetes has been related to several long-term complications and multiple organ failures, including nephropathy, which can lead to kidney failure, retinopathy with the potential loss of vision, and cardiovascular symptoms. Current commercially available synthetic glucose-lowering agents have been reported to have several adverse effects. Therefore, the search for alternative remedies such as medicinal plants and their active compounds have attracted attention. Chrysin is an active flavonoid that exists widely in various plants and diets and has been reported to possess pharmacological properties, including antidiabetic activity. Many studies have been conducted to characterize the antidiabetic of chrysin, as well as its potential pathways, in in vitro and in vivo experiments. Chrysin has shown promise as an antidiabetic agent in animal studies, thus, demonstrating its potential to be developed as an antidiabetic drug. This review discussed the antidiabetic action of chrysin and its mechanisms, including targeting different mechanisms such as stimulation of insulin signaling, blockage of endoplasmic reticulum stress and oxidative damage, promotion of skeletal glucose uptake, as well as modulation of apoptosis and autophagy signaling. Additionally, this review would be useful for further studies regarding the mechanism of work of plant derived-compound as a potential antidiabetic agent.
Zeitschrift für Naturforschung C
The emergence of antibacterial resistance has significantly increased. Pseudomonas aeruginosa is ... more The emergence of antibacterial resistance has significantly increased. Pseudomonas aeruginosa is associated with nosocomial infection and difficult to control. Artocarpin, a flavonoid from Artocarpus heterophyllus Lam. exhibits several pharmacological properties including antibacterial. The study was performed to evaluate interaction between artocarpin and antibiotics including tetracycline against P. aeruginosa. Its mechanism of action on membrane permeability was also investigated. Broth microdilution was conducted for the susceptibility assay. The interaction of artocarpin and antibiotics was evaluated using checkerboard method, the effect on alteration of membrane cell was investigated using bacteriolysis and the released of 260 nm materials. Artocarpin showed moderate to weak activity against the Gram-negative bacteria including P. aeruginosa with MIC values in the range of 31.25–250 μg/mL. A synergistic effect against P. aeruginosa was produced by the combination of artocarpin...
Nutrients, Dec 3, 2016
Diabetic retinopathy (DR) develops in a significant proportion of patients with chronic diabetes,... more Diabetic retinopathy (DR) develops in a significant proportion of patients with chronic diabetes, characterized by retinal macular edema and abnormal retinal vessel outgrowth leading to vision loss. Chrysin, a naturally-occurring flavonoid found in herb and honeycomb, has anti-inflammatory, antioxidant, and anti-cancer properties. This study sought to determine the protective effects of chrysin on retinal neovascularization with abnormal vessels and blood-retinal barrier (BRB) breakdown in 33 mM glucose-exposed human retinal endothelial cells and in db/db mouse eyes. High glucose caused retinal endothelial apoptotic injury, which was inhibited by submicromolar chrysin. This compound diminished the enhanced induction of HIF-1α, vascular endothelial growth factor (VEGF), and VEGF receptor-2 (VEGFR2) in high glucose-exposed retinal endothelial cells. Consistently, oral administration of 10 mg/kg chrysin reduced the induction of these proteins in db/db mouse eye tissues. In addition, chrysin restored the decrement of VE-cadherin and ZO-1 junction proteins and PECAM-1 in hyperglycemia-stimulated retinal endothelial cells and diabetic mouse retina, possibly maintaining tight cell-cell interactions of endothelial cells and pericytes. Anti-apoptotic chrysin reduced the up-regulation of Ang-1, Ang-2, and Tie-2 crucial to retinal capillary occlusion and BRB permeability. Furthermore, orally treating chrysin inhibited acellular capillary formation, neovascularization, and vascular leakage observed in diabetic retinas. These observations demonstrate, for the first time, that chrysin had a capability to encumber diabetes-associated retinal neovascularization with microvascular abnormalities and BRB breakdown.
Acta pharmacologica Sinica, Jan 15, 2017
Glomerular epithelial podocytes are highly specialized cells that play a crucial role in maintain... more Glomerular epithelial podocytes are highly specialized cells that play a crucial role in maintaining normal function of the glomerular filtration barrier via their foot processes. Chrysin (5,7-dihydroxyflavone) is a natural flavonoid found in propolis and mushrooms that has anti-inflammatory, antioxidant and anticancer properties. This study aimed to evaluate the renoprotective effects of chrysin on podocyte apoptotic loss and slit diaphragm protein deficiency in high glucose-exposed podocytes and in db/db mouse kidneys. Exposure to high glucose (33 mmol/L) caused glomerular podocyte apoptosis in vitro, which was dose-dependently attenuated by nontoxic chrysin (1-20 μmol/L) through reduction of DNA fragmentation. Chrysin treatment dose-dependently restored the increased Bax/Bcl-2 ratio, and suppressed Apaf-1 induction and the elevated cytochrome c release in high glucose-exposed renal podocytes. In diabetic db/db mice, oral administration of chrysin (10 mg·kg(-1)·d(-1), for 10 weeks...
Journal of Agricultural and Food Chemistry, 2017
Lung inflammation and oxidative stress are the major contributors to the development of obstructi... more Lung inflammation and oxidative stress are the major contributors to the development of obstructive pulmonary diseases. Macrophages are involved in pulmonary inflammation and alveolar damage in emphysema. Astragalin is an anti-inflammatory flavonoid present in persimmon leaves and green tea seeds. This study elucidated that astragalin inhibited inflammatory cell infiltration induced by 20 μM H2O2 and blocked airway thickening and alveolar emphysema induced by 20 μg of ovalbumin (OVA) in mice. OVA induced mouse pulmonary MCP-1, and H2O2 enhanced the expression of MCP-1/ICAM-1/αv integrin in bronchial airway epithelial BEAS-2B cells. Such induction was inhibited by supplying 10-20 mg/kg of astragalin to OVA-challenged mice and 1-20 μM astragalin to oxidant-stimulated cells. Oral administration of 20 mg/kg of astragalin reduced the induction of F4/80/CD68/CD11b in airways of mice challenged with OVA. Additionally, emphysema tissue damage was observed in OVA-exposed alveoli. Mast cell recruitment in the airway subepithelium was blocked by supplementing astragalin to OVA-challenged mice. Orally treating 20 mg/kg of astragalin reduced α-SMA induction in inflammation-occurring airways and appeared to reverse airway thickening and constriction induced by an OVA episode. These results revealed that astragalin may improve airway thickening and alveolar destruction with blockade of allergic inflammation in airways. Therefore, astragalin may be a therapeutic agent antagonizing asthma and obstructive pulmonary diseases.
Oncotarget, 2017
Macrophage apoptosis is salient in advanced atherosclerotic lesions and is induced by several sti... more Macrophage apoptosis is salient in advanced atherosclerotic lesions and is induced by several stimuli including endoplasmic reticulum (ER) stress. This study examined that α-asarone present in purple perilla abrogated macrophage injury caused by oxysterols via ER stress-and autophagy-mediated mechanisms. Nontoxic α-asarone at 1-20 μM attenuated 7β-hydroxycholesterol-induced activation of eukaryotic initiation factor 2α in macrophages leading to C/EBP homologous protein (CHOP) expression and apoptosis due to sustained ER stress. The α-asarone treatment increased the formation of autophagolysosomes localizing in perinuclear regions of 7β-hydroxycholesterol-exposed macrophages. Consistently, this compound promoted the induction of the key autophagic proteins of beclin-1, vacuolar protein sorting 34 and p150 responsible for vesicle nucleation, and prompted the conversion of microtubule-associated protein 1A/1B-light chain 3 and the induction of p62, neighbor of BRCA1 and autophagy-related (Atg) 12-Atg5-Atg16L conjugate involved in phagophore expansion and autophagosome formation. Additionally, α-asarone increased ER phosphorylation of bcl-2 facilitating beclin-1 entry to autophagic process. Furthermore, the deletion of Atg5 or beclin-1 gene enhanced apoptotic CHOP induction. Collectively, α-asarone-stimulated autophagy may be potential multitargeted therapeutic avenues in treating ER stress-associated macrophage apoptosis.
Osteoporosis is one of the most prevalent forms of age-related bone diseases. Increased bone loss... more Osteoporosis is one of the most prevalent forms of age-related bone diseases. Increased bone loss with advancing age has become a grave public health concern. This study examined whether phlorizin and phloretin, dihydrochalcones in apple peels, inhibited senile osteoporosis through enhancing osteoblastogenic bone formation in cell-based and aged mouse models. Submicromolar phloretin and phlorizin markedly stimulated osteoblast differentiation of MC3T3-E1 cells with increased transcription of Runx2 and osteocalcin. Senescence-accelerated resistant mouse strain prone-6 (SAMP6) mice were orally supplemented with 10 mg/kg phlorizin and phloretin daily for 12 weeks. Male senescence-accelerated resistant mouse strain R1 mice were employed as a nonosteoporotic age-matched control. Oral administration of ploretin and phorizin boosted bone mineralization in all the bones of femur, tibia and vertebra of SAMP6. In particular, phlorizin reduced serum RANKL/OPG ratio and diminished TRAP-positive osteoclasts in trabecular bones of SAMP6. Additionally, treating phlorizin to SAMP6 inhibited the osteoporotic resorption in distal femoral bones through up-regulating expression of BMP-2 and collagen-1 and decreasing production of matrix-degrading cathepsin K and MMP-9. Finally, phlorizin and phloretin antagonized GSK-3β induction and β-catenin phosphorylation in osteoblasts and aged mouse bones. Therefore, phlorizin and phloretin were potential therapeutic agents encumbering senile osteoporosis through promoting bone-forming osteoblastogenesis via modulation of GSK-3β/β-catenin-dependent signaling.
Gossypetin, usually isolated from the flowers and the calyx of Hibiscus sabdariffa, possesses ant... more Gossypetin, usually isolated from the flowers and the calyx of Hibiscus sabdariffa, possesses anti-microbial and anti-atherosclerotic effects. However, anti-osteoporotic effects of gossypetin have not been elucidated. Gossypetin attenuated RANKL-induced multinucle-ated osteoclast formation with enhanced TRAP activity and blunted bone resorption active in osteoclasts. Gossypetin inhibited the actin ring formation and αvβ3 integrin induction for sealing zones. This compound suppressed the induction of CAII, V-ATPase, ClC-7 and Ae2, all required for secretion of proton and chloride ions into resorption lacunae. Furthermore , gossypetin reduced lysosomal cathepsin K transcription and MMP-9 activity, blunting accumulation of lysosomes in osteoclasts displaying an actin ring. The presence of gossypetin deterred the induction of Rab7, and Atg12–Atg5 conjugate and Atg7 involved in LC3 lipidation, all prerequisites to osteoclast ruffled border formation. These observations demonstrate for the first time that gossypetin was effective in retarding ruffled border formation and acidi-fication in a sealed microenvironment of osteoclast resorption lacunae.
Keterbatasan kontrol positif untuk pemeriksaan spesies malaria secara molekuler dengan teknik
Pol... more Keterbatasan kontrol positif untuk pemeriksaan spesies malaria secara molekuler dengan teknik
Polymerase Chain Reaction (PCR), mendorong kita mencari cara alternatif dengan metode
kloning. Metode kloning dilakukan untuk perbanyakan DNA Plasmodium spp. terutama spesies
yang belum dapat dikembangbiakkan secara kultur berkesinambungan. Amplifikasi DNA
Plasmodium spp. menggunakan metode single round dan nested PCR yang selanjutnya produk
PCR tersebut digunakan sebagai DNA target dalam proses kloning. Proses kloning meliputi ligasi
ke dalam TOPO vektor, transformasi ke dalam host Escherichia coli DH5α kompeten, dan seleksi
hasil transformasi pada media selektif. Selanjutnya dilakukan lagi PCR spesiasi sebagai tahap
akhir untuk mengecek keberhasilan kloning. Metode single round PCR menghasilkan produk
DNA dengan ukuran panjang basa 200-300 bp, sedangkan metode nested PCR menghasilkan
produk DNA berukuran 100-200 bp. Keuntungan metode kloning adalah dapat menghasilkan
produk DNA dengan jumlah banyak dari volume sampel yang sedikit dan waktu yang relatif
singkat. Jika dibandingkan dengan DNA parasit dari hasil kultur berkesinambungan, penggunaan
DNA hasil kloning sebagai kontrol positif hanya terbatas pada satu metode PCR saja. Selain itu
tes lanjutan untuk menguji stabilitas produk kloning juga sangat diperlukan.
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Papers by Lucia Dwi Antika
Polymerase Chain Reaction (PCR), mendorong kita mencari cara alternatif dengan metode
kloning. Metode kloning dilakukan untuk perbanyakan DNA Plasmodium spp. terutama spesies
yang belum dapat dikembangbiakkan secara kultur berkesinambungan. Amplifikasi DNA
Plasmodium spp. menggunakan metode single round dan nested PCR yang selanjutnya produk
PCR tersebut digunakan sebagai DNA target dalam proses kloning. Proses kloning meliputi ligasi
ke dalam TOPO vektor, transformasi ke dalam host Escherichia coli DH5α kompeten, dan seleksi
hasil transformasi pada media selektif. Selanjutnya dilakukan lagi PCR spesiasi sebagai tahap
akhir untuk mengecek keberhasilan kloning. Metode single round PCR menghasilkan produk
DNA dengan ukuran panjang basa 200-300 bp, sedangkan metode nested PCR menghasilkan
produk DNA berukuran 100-200 bp. Keuntungan metode kloning adalah dapat menghasilkan
produk DNA dengan jumlah banyak dari volume sampel yang sedikit dan waktu yang relatif
singkat. Jika dibandingkan dengan DNA parasit dari hasil kultur berkesinambungan, penggunaan
DNA hasil kloning sebagai kontrol positif hanya terbatas pada satu metode PCR saja. Selain itu
tes lanjutan untuk menguji stabilitas produk kloning juga sangat diperlukan.
Polymerase Chain Reaction (PCR), mendorong kita mencari cara alternatif dengan metode
kloning. Metode kloning dilakukan untuk perbanyakan DNA Plasmodium spp. terutama spesies
yang belum dapat dikembangbiakkan secara kultur berkesinambungan. Amplifikasi DNA
Plasmodium spp. menggunakan metode single round dan nested PCR yang selanjutnya produk
PCR tersebut digunakan sebagai DNA target dalam proses kloning. Proses kloning meliputi ligasi
ke dalam TOPO vektor, transformasi ke dalam host Escherichia coli DH5α kompeten, dan seleksi
hasil transformasi pada media selektif. Selanjutnya dilakukan lagi PCR spesiasi sebagai tahap
akhir untuk mengecek keberhasilan kloning. Metode single round PCR menghasilkan produk
DNA dengan ukuran panjang basa 200-300 bp, sedangkan metode nested PCR menghasilkan
produk DNA berukuran 100-200 bp. Keuntungan metode kloning adalah dapat menghasilkan
produk DNA dengan jumlah banyak dari volume sampel yang sedikit dan waktu yang relatif
singkat. Jika dibandingkan dengan DNA parasit dari hasil kultur berkesinambungan, penggunaan
DNA hasil kloning sebagai kontrol positif hanya terbatas pada satu metode PCR saja. Selain itu
tes lanjutan untuk menguji stabilitas produk kloning juga sangat diperlukan.