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Our effort to find new material for anti cancer from natural resources leads us to focus on stingless bee products such as honey, bee pollen, and propolis. The products were from seven stingless bees named Homotrigona fimbriata, Heterotrigona itama, Heterotrigona bakeri, Tetragonula sarawakensis, Tetragonula testaceitarsis, Tetragonula fuscobalteata, Tetragonula laeviceps. The stingless bee products were evaluated for their cytotoxicity effect on MCF-7, HeLa and Caco-2 cancer cell lines. This is the first time to be reported that the honey, ethanol extracts of bee pollen and propolis of H. fimbriata displayed more potent cytotoxicity than other stingless bee products. By chromatography and biological activity-guided fractionation, ethanol extract of propolis from H. fimbriata was fractionated and isolated its active compound named mangiferonic acid. Mangiferonic acid showed a cytotoxicity effect with IC50 values 96.76 µM in MCF-7, >110.04 µM in HeLa, and > 110.04 µM in Caco-2, respectively. These results exhibited the potential of ethanol extracts from propolis of H. fimbriata to be further developed for drug and experiments to verify the function are essential.

Extracellular basic pH regulates cellular processes in wounds, and consequently influenced wound healing. Oxidative defence system modulation in the skin helps heal wounds, inhibits skin ageing and improves the skin condition. Moreover, the role of keratinocyte growth factor (KGF) and nuclear factor erythroid 2‐related factor 2 (Nrf2) in antioxidant systems has been reported in various skin models. However, the effects of extracellular basic pH on wound‐ or skin ageing‐related skin damage have not been examined. Thus, we investigated the antioxidant systems affected by extracellular basic pH in a 3D human skin equivalent system (3HSE). Extracellular basic pH decreased KGF expression and enhanced the oxidative defence system, and thus activated Nrf2 in the 3HSE. Additionally, extracellular basic pH and KGF treatment up‐regulated Nrf2 activation and its regulation of the oxidative defence system in the 3HSE. This indicates that Nrf2 up‐regulation is enhanced by reactive oxygen species production, rather than KGF, and by extracellular basic pH of the skin. The inhibition of skin damage through pH imbalance and KGF regulation suggests that the development of pH‐regulating or pH‐maintaining materials may provide effective therapeutic strategies for maintaining a healthy skin.

Allergic dermatitis (AD) clinically presents with skin erythematous plaques, eruption, and elevated serum IgE, and T helper cell type 2 and 1 (Th2 and Th1) cytokine levels. 6-Shogaol [1-(4-hydroxy-methoxyphenyl)-4-decen-one], a pungent compound isolated from ginger, has shown anti-inflammatory effects, but its inhibitory effects on AD are unknown. The aim of this study was to examine whether 6-shogaol inhibits AD-like skin lesions and their underlying mechanism in vivo and in vitro. An AD-like response was induced by tumor necrosis factor-α (TNF-α)+IFN-γ in human keratinocytes or by 2,4-dinitrochlorobenzene (DNCB) in mice. In vivo, 6-shogaol inhibited the development of DNCB-induced AD-like skin lesions and scratching behavior, and showed significant reduction in Th2/1-mediated inflammatory cytokines, IgE, TNF-α, IFN-γ, thymus and activation-regulated chemokine, IL-1, 4, 12, and 13, cyclooxygenase-2, and nitric oxide synthase levels. In vitro, 6-shogaol inhibited reactive oxygen species (ROS) and mitogen-activated protein kinases (MAPKs) signaling, and increased the levels of total glutathione, heme oxygenase-1, and quinone 1 via nuclear factor erythroid 2 related factor 2 (Nrf2) activation. 6-Shogaol can alleviate AD-like skin lesions by inhibiting immune mediators via regulating the ROS/MAPKs/Nrf2 signaling pathway, and may be an effective alternative therapy for AD.

Background: Oxidative radicals are major environmental causes of human skin damage. Oxidative defense factors, including nuclear factor erythroid-derived 2-related factor 2 (Nrf2), are centrally involved in repairing skin cells or protecting them from oxidative damage. Coriandrum sativum L. (coriander; CS) is a commonly consumed food and a traditional phytomedicine in Asia and Europe. In this study, we examined the protective effects of a standardized CS leaf extract against oxidative stress in human HaCaT keratinocytes. Methods and Results: CS significantly and dose-dependently protected cells against reduced cell viability caused by H2O2-induced damage, as assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Other assays demonstrated that CS protected HaCaT cells by increasing the levels of glutathione and activities of oxidative defense enzymes, such as superoxide dismutase and catalase. Moreover, it increased the expression of activated Nrf2, which plays a crucial role in protecting skin cells against oxidative stress. Conclusion: These results suggest that CS protects human keratinocytes from H2O2-induced oxidative stress through antioxidant effects.

This study was performed to investigate effects of Curculigo orchioides rhizome (curculiginis rhizome) on acute reflux esophigitis (RE) in rats that are induced by pylorus and forestomach ligation operation. Proinflammatory cytokine, as well as tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 were all assayed and the expression of TNF-α and COX2 analyzed by RT-PCR. The esophagic tissue damage of reflux esophagitis rat was increased compared to that of normal intact group. However, the esophagic damage percentage from the extract of curculiginis rhizoma (ECR) 600 mg/kg and ECR 300 mg/kg were significantly lower than that of the RE control group. Administration of α-tocopherol (30 mg/kg) and ECR (600 mg/kg, 300 mg/kg, and 150 mg/kg) had a significant effect on the gastric acid pH in rats with induced reflux esophagitis (p < 0.05). The treatment with ECR significantly reduced the production of cytokines TNF-α, IL-1β and IL-6 levels compared to the model group (p < 0.05). The expression of TNF-α and COX2 in the intact esophageal mucosa was low while those of the RE control group were significantly higher due to an inflammatory reaction in the esophagus. Compare to the model group, treatment with α-tocopherol or ECR significantly inhibited the expression levels of COX2 and TNF-α in a dose-dependent manner. These results suggest that anti-inflammatory and protective effects of ECR could attenuate the severity of reflux esophagitis and prevent esophageal mucosal damage.

Extracts of Indonesian medicinal plants, Murraya koenigii, Syzygium polyanthum, and Zingiber purpurea were investigated for their biological activity. The presence of phytochemicals, cytotoxicity, and antimicrobial and antioxidant activities were investigated. Parts of M. koenigii, S. polyanthum, and Z. purpurea were extracted with ethanol. The extracts were evaluated for antimicrobial activity using the disc diffusion method, while antioxidant activity was determined with a 1,1-diphenyl-2-picrylhydrazyl radical scavenging assay. Cytotoxicity was investigated using the brine shrimp lethality test, and phytochemical screening was performed using a standard method. M. koenigii leaf extract exhibited the most activity in the test microorganism activity index (AI), 0.38-1.25, when compared with standard drugs. S. polyanthum ripened fruit displayed significant antioxidant activity (90%) in comparison to ascorbic acid (95%). Z. purpurea rhizome extract possessed the highest cytotoxic effect with a LC50 of 52 μg/mL. Phytochemical analysis revealed that carbohydrate, tannin, alkaloid, steroid, triterpenoid, and flavonoid were present in the extracts of M. koenigii leaves and twigs, S. polyanthum leaves and ripened and unripe fruits, and Z. purpurea rhizome, while saponin was only present in the S. polyanthum ripened fruit extract. Our work revealed that the M. koenigii leaves, S. polyanthum ripened fruit, and Z. purpurea rhizome extracts have potential as sources of new antimicrobial, antioxidant, and cytotoxic compounds, respectively.

An active compound from the bulb of Eleutherine americana L. Merr. (Iridaceae) collected from East Kalimantan, Indonesia, was tested for its antidermatophyte and antimelanogenesis activity. Antifungal assay-directed fractionation of the n-hexane-soluble fraction of the methanolic extract of the bulb of E. americana led to the isolation of 1 as an active compound. The compound was identified as the naphthoquinone eleutherin by EI-MS and (1)H-, (13)C-, and two-dimensional NMR analyses. Antidermatophyte assay of 1 at concentrations of 10, 20, 40, 60, and 80 microg/disk and myconazole, a commercial antidermatophyte, at 10 microg/disk displayed 7, 8, 13, 16, 17, and 14 mm of inhibition zone against Trichophyton mentagrophytes, respectively. In a melanin formation inhibition assay, compound 1 displayed potent antimelanogenesis activity at 5 ppm with low toxicity compared with arbutin, a commercial skin-whitening agent. The results showed the high potential of 1, an active compound from E. americana, to be applied as an antidermatophyte and antimelanogenesis agent.

Background/Aims: Wound healing is a complex regeneration process involving the degradation and reassembly of connective tissues and skin layers. Previous studies have shown that pH plays a significant role in both the direct and indirect regulation of cellular processes in the wound, which, in turn, affect the wound healing process. However, the effects of pH on the collagen breakdown component of wound healing have yet to be investigated. Therefore, we investigated the induction of accelerated collagen breakdown by pH imbalance in the skin. Methods: Na+/H+ exchanger and metalloproteinase (MMP)-1 were analyzed spectrophotometrically, and the expression of collagen type-I-alpha-1 (COL1A1) and mitogen-activated protein kinase (MAPK) was measured by Western blotting. Results: Accelerated collagen breakdown induced by extracellular basic pH via the overproduction of reactive oxygen species (ROS) and MAPK signaling was examined in skin fibroblasts and in a three-dimensional human skin equivalent system. Basic pH (>7.50) upregulated MMP-1 and downregulated COL1A1 levels via ROS generation and MAPK signaling pathways. Acidic pH (Conclusion: Our results indicate that skin pH is an important effector of collagen formation in wound healing. This finding will aid in the development of new pH-targeted therapeutic strategies.

A new pentacoordinated ferrous compound [TPAFeCl]+ (TPA = tris(2-pyridylmethyl)amine) was synthesized from the reaction between H3TPA(ClO4)3 and Fe(PnPr3)2Cl2 in MeCN. The unique trigonal bipyramidal [TPAFeCl]+ complex was characterized as a S = 2 high spin complex based on the crystallographic structure, magnetic susceptibility, 1H NMR spectrum and semi-empirical ZINDO/S calculations. Crystal of [TPAFeCl]2(FeCl4)(MeCN)2 was monoclinic with a = 12.019(2) A, b = 27.550(5) A, c = 14.138(2) A, β = 94.168(3)°, V = 4668.9(13) A3, space group C/c, and the unit cell contained a racemic mixture of Δ and Λ isomers with ferrous tetrachloride anion.

Cyclin-dependent kinase 2 (Cdk2) activity is thought to be involved in cell death-associated chromatin condensation and other manifestations of apoptotic death. Here we show that during TNFalpha-induced apoptosis, PKCdelta is activated in a caspase-3-dependent manner and phosphorylates p21(WAF1/CIP1), a specific cyclin-dependent kinase inhibitor, on (146)Ser. This residue is located near a cyclin-binding motif (Cy2) that plays an important role in the interaction between p21(WAF1/CIP1) and Cdk2, and its phosphorylation modulates the ability of p21(WAF1/CIP1) to associate with Cdk2. The phosphorylation of p21(WAF1/CIP1) is temporally related to the activation kinetics of Cdk2 activity during the apoptosis. We propose that during TNFalpha-induced apoptosis, PKCdelta-mediated phosphorylation of p21(WAF1/CIP1) at (146)Ser attenuates the Cdk2 binding of p21(WAF1/CIP1) and thereby upregulates Cdk2 activity.

Purpose : To investigate the antioxidant and anti-melanogenesis activities of Durio kutejensis [Bombacaceae (Hassk.) Becc] fruit extract. Methods : The fruit flesh of D. kutejensis was extracted successively with n-hexane, ethyl acetate/EtOAc, and ethanol/EtOH at room temperature repeatedly. The extracts were concentrated in vacuo to yield their residues. Antioxidant properties were analyzed by 2,2'-azino-bis(3- ethylbenzothiazoline-6-sulphonic acid) (ABTS, superoxide dismutase (SOD)-like activity, 2,2-diphenyl-1- picrylhydrazyl (DPPH), and oxygen radical absorbance capacity (ORAC) while anti-melanogensis activity was evaluated by tyrosinase enzyme activity and B16 melanoma cell assays (melanin inhibition and cytotoxicity). Results : The extract (200 μg/mL) showed melanin inhibition by inhibiting melanin formation in B16 melanoma cell by 47 % without cytotoxicity but did not inhibit tyrosinase enzyme activity. The extract (1 - 1000 μg/mL) also exhibited some level of antioxidant activity including ORAC (0.04 ± 0.00 μmol TE/mg at 950 μg/mL), ABTS (1.0 ± 0.2 % at 100.8 μg/mL), SOD (IC50, 76.00 ± 14.6 μg/mL, and DPPH (21.5 ± 0.7 % at 97.39 μg/mL extract concentration). Conclusion : The fruit extract of Durio kutejensis has antioxidant properties with a potential for treating hyperpigmentation and for use as a skin-lightening agent. Keywords : Durio kutejensis , Antioxidant, Anti-melanogenesis, B16 Melanoma cell Hyperpigmentation, Skin-lightening agent

We investigated the leaves of Kleinhovia hospita , a plant which has been traditionally used in Indonesia as phytotherapy to cure liver disease, to describe antioxidant materials from plant sources. K. hospita leaves were extracted with methanol and further partitioned into n -hexane, diethyl ether, and ethyl acetate. The antioxidant activity of each fraction and the residue was assessed using a 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging method and their cytotoxicity on HepG2 liver cancer cells was determined by a MTT assay. The K. hospita leaf methanol extract showed strong antioxidant activity (96%) compared with vitamin C (98%) by the DPPH method and the measured activity from the subsequent extracts of the methanol extract were 48.9% for n -hexane, 74.0% for diethyl ether, 84.3% for ethyl acetate, and 77.1% for the residue. The MTT assay showed the cytotoxicity of the methanol extract on HepG2 cells at 14%, 76%, and 80% at concentrations of 50μg/mL, 87.5μg/mL, and 125μg/mL, respectively. Leaf extracts of the medicinal plant K. hospita showed potent antioxidant activity and moderate cytotoxicity on HepG2 liver cancer cells.

We investigated medicinal plant sources with 5alpha-reductase inhibitory activity. These compounds have been used in several remedies against androgen-dependent diseases including benign prostatic hyperplasia. The 50% ethanol extract of Polygonum multiflorum Thunb (Polygoni Multiflori Radix; Polygonaceae) showed potent 5alpha-reductase inhibitory activity. The fraction responsible for this activity was purified, and the active constituent was isolated and identified as emodin, an anthraquinone compound. Although emodin showed considerably less potent inhibitory activity than riboflavin, the inhibitory activity of the compound was more potent than that of alizarin (1,2-dihydroxyanthraquinone), an anthraquinone-type positive control. Also, anthraquinone itself was substantially inactive against 5alpha-reductase, in dicating that the hydroxyl group on the structure of emodin is an important structural moiety for displaying inhibitory activity.