Isolation of New Diterpenoids from the Halophyte, Vitex rotundifolia, and their Antioxidant and Anti-inflammatory Activities.

In this study, three diterpenoids (1-3), including one known compound (1), were isolated from the fruits of Vitex rotundifolia and their structures were determined via spectroscopic analysis. In lipopolysaccharide-stimulated RAW264.7 cells, these compounds dose-dependently decreased the intracellular reactive oxygen species levels and nitric oxide production compared to those in the control cells. At 25 µM/mL, these compounds also diminished the protein expression of the pro-inflammatory cytokines, inducible nitric oxide synthase, cyclooxygenase-2, and interleukin-6, with compound 3 exhibiting the most potent inhibitory effect.

Structural, electronic, optical, elastic, thermodynamic and thermal transport properties of Cs2AgInCl6 and Cs2AgSbCl6 double perovskite semiconductors using a first-principles study.

In this study, we employ the framework of first-principles density functional theory (DFT) computations to investigate the physical, electrical, bandgap and thermal conductivity of Cs2AgInCl6-CAIC (type I) and Cs2AgSbCl6-CASC (type II) using the GGA-PBE method. CAIC possesses a direct band gap energy of 1.812 eV, while CASC demonstrates an indirect band gap energy of 0.926 eV. The CAIC and CASC exhibit intriguingly reduced thermal conductivity, which can be attributed to the notable reduction in their respective Debye temperatures, measuring 182 K and 135 K, respectively. The Raman active modes computed under ambient conditions have been compared with real-world data, showing excellent agreement. The thermal conductivity values of CAIC and CASC compounds exhibit quantum mechanical characteristics, with values of 0.075 and 0.25 W m-1 K-1, respectively, at 300 K. It is foreseen that these outcomes will generate investigations concerning phosphors and diodes that rely on single emitters, with the aim of advancing lighting and display technologies in the forthcoming generations.

Correction: Structural, electronic, optical, elastic, thermodynamic and thermal transport properties of Cs2AgInCl6 and Cs2AgSbCl6 double perovskite semiconductors using a first-principles study.

Correction for 'Structural, electronic, optical, elastic, thermodynamic and thermal transport properties of Cs2AgInCl6 and Cs2AgSbCl6 double perovskite semiconductors using a first-principles study' by Keqing Zhang et al., Phys. Chem. Chem. Phys., 2023, 25, 31848-31868, https://doi.org/10.1039/d3cp03795a.

Effect of D-pinitol on MK-801-induced schizophrenia-like behaviors in mice.

Schizophrenia is a chronic brain disorder characterized by positive symptoms (delusions or hallucinations), negative symptoms (impaired motivation or social withdrawal), and cognitive impairment. In the present study, we explored whether D-pinitol could ameliorate schizophrenia-like behaviors induced by MK-801, an N-methyl-D-aspartate receptor antagonist. Acoustic startle response test was conducted to evaluate the effects of D-pinitol on sensorimotor gating function. Social interaction and novel object recognition tests were employed to measure the impact of D-pinitol on social behavior and cognitive function, respectively. Additionally, we examined whether D-pinitol affects motor coordination. Western blotting was conducted to investigate the mechanism of action of D-pinitol. Single administration of D-pinitol at 30, 100, or 300 mg/kg improved the sensorimotor gating deficit induced by MK801 in the acoustic startle response test. D-Pinitol also reversed social behavior deficits and cognitive impairments induced by MK-801 without causing any motor coordination deficits. Furthermore, D-pinitol reversed increased expression levels of pNF-kB induced by MK-801 treatment and consequently increased expression levels of TNF-α and IL-6 in the prefrontal cortex. These results suggest that D-pinitol could be a potential candidate for treating sensorimotor gating deficits and cognitive impairment observed in schizophrenia by down-regulating transcription factor NF-κB and pro-inflammatory cytokines in the prefrontal cortex.

Inhibitory Effects of Sesquiterpenoids Isolated from Artemisia scoparia on Adipogenic Differentiation of 3T3-L1 Preadipocytes.

Obesity and related complications are significant health issues in modern society, largely attributed to a sedentary lifestyle and a carbohydrate-rich diet. Since anti-obesity drugs often come with severe side effects, preventative measures are being sought globally, including dietary changes and functional foods that can counteract weight gain. In this context, plant-based metabolites are extensively studied for their advantageous biological effects against obesity. Several plants within the Artemisia genus have been reported to possess anti-adipogenic properties, preventing adipocytes from maturing and accumulating lipids. The present study investigated the anti-adipogenic potential of two sesquiterpenoids, reynosin and santamarine, isolated from A. scoparia in adipose-induced 3T3-L1 preadipocytes. Differentiating 3T3-L1 adipocytes treated with these isolated compounds displayed fewer adipogenic characteristics compared to untreated mature adipocytes. The results indicated that cells treated with reynosin and santamarine accumulated 55.0% and 52.5% fewer intracellular lipids compared to untreated control adipocytes, respectively. Additionally, the mRNA expression of the key adipogenic marker, transcription factor PPARγ, was suppressed by 87.2% and 91.7% following 60 µM reynosin and santamarine treatment, respectively, in differentiated adipocytes. Protein expression was also suppressed in a similar manner, at 92.7% and 82.5% by 60 µM reynosin and santamarine treatment, respectively. Likewise, SERBP1c and C/EBPα were also downregulated at both gene and protein levels in adipocytes treated with samples during differentiation. Further analysis suggested that the anti-adipogenic effect of the compounds might be a result of AMPK activation and the subsequent suppression of MAPK phosphorylation. Overall, the present study suggested that sesquiterpenoids, reynosin, and santamarine were two potential bioactive compounds with anti-adipogenic properties. Further research is needed to explore other bioactive agents within A. scoparia and elucidate the in vivo action mechanisms of reynosin and santamarine.

Quercetin 3-O-Galactoside Isolated from Limonium tetragonum Inhibits Melanogenesis by Regulating PKA/MITF Signaling and ERK Activation.

Quercetin 3-O-galactoside (Q3G) is a common dietary flavanol that has been shown to possess several bioactivities, including anti-melanogenesis. However, how Q3G exerts its anti-melanogenic effect has not been studied. The current study, therefore aimed to investigate the anti-melanogenesis potential of Q3G and elucidate the underlying action mechanism in α-melanocyte-stimulating hormone (α-MSH)-induced hyperpigmentation model of B16F10 murine melanoma cells. Results showed that α-MSH stimulation significantly increased tyrosinase (TYR) and melanin production, which were significantly downregulated by Q3G treatment. The treatment with Q3G suppressed the transcriptional and protein expressions of melanogenesis-related enzymes TYR, tyrosinase related protein-1 (TRP-1), and TRP-2, along with the melanogenic transcription factor microphthalmia-associated transcription factor (MITF) in B16F10 cells. It was shown that Q3G downregulated MITF expression and suppressed its transcriptional activity by inhibiting the cAMP-dependent protein kinase A (PKA)-mediated activation of CREB and GSK3ß. In addition, MAPK-regulated MITF activation signaling was also involved in the inhibition of melanin production by Q3G. The results suggest that the anti-melanogenic properties of Q3G rationalize further studies in vivo to confirm its action mechanism and consequent utilization as a cosmetic ingredient against hyperpigmentation.

Oleracone C from Portulaca oleracea attenuates UVB-induced changes in matrix metalloproteinase and type I procollagen production via MAPK and TGF-ß/Smad pathways in human keratinocytes.

BACKGROUND: Chronic exposure to ultraviolet (UV) radiation induces photo-oxidation, which in turn causes the overproduction of matrix metalloproteinases (MMPs) and collagen degradation. These symptoms are referred to as photoaging, which is characterized by skin thickness, irregular pigmentation, elastosis and coarse wrinkles. In this study, the protective effects of oleracone C isolated from Portulaca olerace against UVB-induced changes in MMPs and type I procollagen production were investigated in human keratinocytes. METHODS: Human immortalized keratinocytes have been used as an in vitro cell model to study the abnormal skin barrier development such as in photoaging. The effects of the compound on cell viability were determined by colorimetric MTT assay. This study also measured ROS production using DCFH-DA assay. Releases of MMPs and type Iα1 procollagen were analysed by ELISA. RT-PCR and Western blot were carried out to test the expressions of mRNA and proteins related to MMPs and type I procollagen biosynthesis. RESULT: Effect of oleracone C against UVB-mediated oxidative stress was evaluated measuring its ability to eliminate UVB-induced activation of reactive oxygen species (ROS). Treatment of oleracone C hindered the production of intracellular ROS. UVB exposure increased MMPs (MMP-1, MMP-2 and MMP-9) release from keratinocytes and decreased the release of type I procollagen. Treatment with oleracone C reversed these effects of UVB exposure. Oleracone C treatment also diminished the intracellular expression of MMP-1, MMP-2 and MMP-9 and elevated the type I procollagen. Oleracone C suppressed the UVB irradiation-dependent upregulation phosphorylation of p38 and ERK1/2 in the mitogen-activated protein kinase (MAPK) pathway. Furthermore, oleracone C stimulated collagen production through the TGF-ß signalling pathway, which activates collagen synthesis in UVB-irradiated keratinocytes. CONCLUSION: These findings reasonably suggest ameliorating the potential of oleracone C against the UVB-induced photoaging of the human keratinocytes.

RÉSUMÉ: CONTEXTE: L'exposition chronique aux rayons ultraviolets (UV) induit la photo-oxydation, qui à son tour entraîne la surproduction de métalloprotéases matricielles (MMP) et la dégradation du collagène. Ces symptômes sont appelés photovieillissement, qui se caractérise par une épaisseur de la peau, une pigmentation irrégulière, une élastose et des rides grossières. Dans cette étude, les effets protecteurs de l'oléracone C isolée à partir du pourpier potager contre les changements induits par les UVB dans les MMP et la production de procollagène de type I ont été étudiés dans les kératinocytes humains. MÉTHODES: Les kératinocytes humains immortalisés ont été utilisés comme modèle cellulaire in vitro pour étudier le développement anormal de la barrière cutanée, comme c'est le cas dans le photovieillissement. Les effets du composé sur la viabilité cellulaire ont été déterminés par test colorimétrique au MTT. Cette étude a également mesuré la production de DRO à l'aide du dosage DCFH-DA. Les productions de MMP et de procollagène de type Iα1 ont été analysées par la méthode ELISA. La RT-PCR et le Western blot ont été réalisés pour tester les expressions de l'ARNm, et des protéines liées aux MMP et à la biosynthèse du procollagène de type I. RÉSULTAT: L'effet de l'oléracone C contre le stress oxydatif médié par les UVB a été évalué en mesurant sa capacité à éliminer l'activation induite par les UVB des dérivés réactifs de l'oxygène (DRO). Le traitement par oléracone C a empêché la production de DRO intracellulaires. L'exposition aux UVB a augmenté la production de MMP (MMP-1, MMP-2 et MMP-9) par les kératinocytes et a diminué la production de procollagène de type I. Le traitement par oléracone C a inversé ces effets de l'exposition aux UVB. Le traitement par oléracone C a également diminué l'expression intracellulaire de MMP-1, MMP-2 et MMP-9, et a augmenté le taux de procollagène de type I. L'oléracone C a supprimé la phosphorylation de régulation à la hausse dépendante de l'exposition aux UVB de p38 et ERK1/2 dans la voie de la protéine kinase activée par des agents mitogènes (Mitogen-Activated Protein Kinase, MAPK). En outre, l'oléracone C a stimulé la production de collagène par la voie de signalisation de TGF-ß, qui active la synthèse du collagène dans les kératinocytes exposés aux UVB. CONCLUSION: Ces résultats indiquent raisonnablement une amélioration du potentiel de l'oléracone C contre le photovieillissement induit par les UVB des kératinocytes humains.

PD-1 inhibitor induces myocarditis by reducing regulatory T cells, activating inflammatory responses, promoting myocardial apoptosis and autophagy.

The present study aimed to explore the pathogenesis of autoimmune myocarditis induced by PD-1 inhibitors and their potential therapeutic targets. Mouse models of autoimmune myocarditis induced by PD-1 inhibitor in mouse models of polymyositis were established. The expression level of PD-1 and regulatory T cells (Tregs), CD4, CD8 + T cells, inflammation, apoptosis and autophagy-related factors, including IL-6, TGF-ß, AMA-M2, Fas/FasL, LC3 and p62 were detected in peripheral blood, muscle or myocardium of mice in each group, using ELISA, RT-PCR, Western Blot and immunofluorescence. In addition, HE and TUNEL staining and ultrastructural scanning were performed on the myocardium of mice in each group. Results showed that the expression level of PD-1 in the two myositis groups was significantly lower than that in the control group, and the level of PD-1 was lower in the myocarditis group than that in the polymyositis group. In the myocardium, TGF-ß, p62, and Tregs proportion showed the same expression level trend as PD-1, while CD8, IL-6, IL-10 and LC3 showed the opposite trend. Levels of Fas/FasL were significantly higher in both myositis groups, but were slightly lower in the myocarditis group, as was AMA-M2. Inflammation, apoptosis, and autophagy were observed in both myositis groups, but were more severe in the myocarditis group. In summary, the decreased expression level of PD-1 leads to decreased Tregs level in the myocardium, aggravated inflammatory response, apoptosis and autophagy, which may be the pathological mechanism of myocarditis induced by PD-1 inhibitors.

Bioaccumulation characteristics, transfer model of heavy metals in soil-crop system and health assessment in plateau region, China.

This study investigated the bioaccumulation and transfer of heavy metals including Cd, Cr, Cu, Mn, Ni, Pb and Zn in soil-crop system in Lhasa, and assessed the health risks of the edible part of the crops. The results showed that the average values of Cd, Cr, Cu, Mn, Ni, Pb and Zn were 0.15, 44.55, 24.68, 532.40, 22.47, 38.18 and 73.99 mg kg-1 in natural soil, and 0.16, 46.93, 38.45, 559.13, 23.23, 40.03 and 83.29 mg kg-1 in cultivated soil, respectively. Highland barley and wheat had the strongest ability to accumulate Zn in grain, the BCF values were 0.24 and 0.27, respectively, significant differences in the distribution of metal contents in crop root, stem, leaf and grain were observed. Root presented larger accumulation capacity in most metals, Zn and Cu was easily transferred in the plant organs, most metals in this study presented difficult to migrate from root to grain. The transfer peak of most metals in soil-crop system appeared from stem to leaf. The concentrations of Cr and Mn in crop grains could be predicted according to the multiple linear regression models. THQ and HI values of heavy metals in edible parts of both highland barley and wheat were below the safety threshold of 1, indicating no detrimental effects posed to adults health. This study helps to understand the accumulation and transfer of heavy metals in soil-crop system in plateau region.

Salidroside, 8(E)-Nuezhenide, and Ligustroside from Ligustrum japonicum Fructus Inhibit Expressions of MMP-2 and -9 in HT 1080 Fibrosarcoma.

A phenyl ethanoid, salidroside (SAL), and two secoiridoids, 8(E)-nuezhenide (NZD) and ligustroside (LIG), were isolated from fruits of Ligustrumjaponicum, used as traditional folk medicine, and their chemical structures were elucidated by the comparison of spectral data with published literature. Matrix metalloproteinases (MMPs) are major enzymes that play crucial roles in the metastasis and invasive behavior of tumors. In particular, MMP-2 and MMP-9, regulated by the MAPK signaling pathways, including p38, ERK and JNK, are known to play a key role in the degradation of the basement membrane. In the present study, the effects of SAL, NZD and LIG on the expression of MMP-2 and -9 were examined in phorbol 12-myristate 13-acetate (PMA)-induced HT 1080 cells. All the compounds significantly lowered the amount of MMP-2 and MMP-9 released, as determined by gelatin zymography and ELISA. In addition, the mRNA and protein expression levels of MMP-2 and MMP-9 were significantly suppressed, as measured by RT-PCR and Western blotting. According to the Western blotting assay, SAL and LIG effectively reduced the expression of MMP-2 in a dose-dependent manner. NZD lowered the expression of MMP-9 in a similar way. The phosphorylation of p38, ERK and JNK was also significantly suppressed by these compounds. These findings suggest that all the compounds regulate the release and expression of MMP-2 and MMP-9 via MAPK signaling pathways.

Libanoridin Isolated from Corydalis heterocarpa Inhibits Adipogenic Differentiation of Bone Marrow-Derived Mesenchymal Stromal Cells.

Bone marrow adiposity is a complication in osteoporotic patients. It is a result of the imbalance between adipogenic and osteogenic differentiation of bone marrow cells. Phytochemicals can alleviate osteoporotic complications by hindering bone loss and decreasing bone marrow adiposity. Corydalis heterocarpa is a biennial halophyte with reported bioactivities, and it is a source of different coumarin derivatives. Libanoridin is a coumarin isolated from C. heterocarpa, and the effect of libanoridin on adipogenic differentiation of human bone marrow-derived mesenchymal stromal cells (hBM-MSCs) was evaluated in the present study. Cells were induced to undergo adipogenesis, and their intracellular lipid accumulation and expression of adipogenic markers were observed under libanoridin treatment. Results showed that 10 µM libanoridin-treated adipocytes accumulated 44.94% less lipid compared to untreated adipocytes. In addition, mRNA levels of PPARγ, C/EBPα, and SREBP1c were dose-dependently suppressed with libanoridin treatment, whereas only protein levels of PPARγ were decreased in the presence of libanoridin. Fluorescence staining of adipocytes also revealed that cells treated with 10 µM libanoridin expressed less PPARγ compared to untreated adipocytes. Protein levels of perilipin and leptin, markers of mature adipocytes, were also suppressed in adipocytes treated with 10 µM libanoridin. Analysis of MAPK phosphorylation levels showed that treatment with libanoridin inhibited the activation of p38 and JNK MAPKs observed by decreased levels of phosphorylated p38 and JNK protein. It was suggested that libanoridin inhibited adipogenic differentiation of hBM-MSCs via suppressing MAPK-mediated PPARγ signaling. Future studies revealing the anti-adipogenic effects of libanoridin in vivo and elucidating its action mechanism will pave the way for libanoridin to be utilized as a nutraceutical with anti-osteoporotic properties.

Dracunculin Inhibits Adipogenesis in Human Bone Marrow-Derived Mesenchymal Stromal Cells by Activating AMPK and Wnt/ß-Catenin Signaling.

Increased bone marrow adiposity is widely observed in patients with obesity and osteoporosis and reported to have deleterious effects on bone formation. Dracunculin (DCC) is a coumarin isolated from Artemisia spp. but, until now, has not been studied for its bioactive potential except antitrypanosomal activity. In this context, current study has reported the anti-adipogenic effect of DCC in human bone marrow-derived mesenchymal stromal cells (hBM-MSCs). DCC dose-dependently inhibited the lipid accumulation and expression of adipogenic transcription factors peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα) in hBM-MSCs induced to undergo adipogenesis. To elucidate its action mechanism, the effect of DCC on Wnt/ß-catenin and AMPK pathways was examined. Results showed that DCC treatment activated Wnt/ß-catenin signaling pathway via AMPK evidenced by increased levels of AMPK phosphorylation and Wnt10b expression after DCC treatment. In addition, DCC treated adipo-induced hBM-MSCs exhibited significantly increased nuclear levels of ß-catenin compared with diminished nuclear PPARγ levels. In conclusion, DCC was shown to be able to hinder adipogenesis by activating the ß-catenin via AMPK, providing potential utilization of DCC as a nutraceutical against bone marrow adiposity.

Clinical outcomes of endoprosthetic reconstruction for proximal femoral resection.

INTRODUCTION: The proximal femur is a common site for primary sarcomas and metastatic lesions. Although the early results of tumor prostheses are promising, the long-term results of reconstruction are unknown. The purpose of this study is to evaluate the prognostic factors affecting prosthesis survival and complications after proximal femoral resection and reconstruction. METHODS: We reviewed the results of 68 patients who underwent proximal femoral resection and reconstruction with a modular bipolar-type tumor prosthesis between 2005 and 2017. The mean follow-up was 55.6 months (range 6-172 months). There were 50 male and 18 female patients with a mean age of 41.5 years (range 11-80 years). Cumulative survival analysis was performed to analyze the risk factors of prosthesis survival. We also evaluated the complications after operation. RESULTS: Fourteen (21%) patients required further surgery at a mean 37 months post-operatively (range 5-125 months). There were three cases of infection (4%), six of local recurrence (9%), three of acetabular erosion (4%) and two of stem loosening (3%). The implant survival rates were 83.9% at 5 years and 59.8% at 10 years. Prosthesis survivals did not differ based on fixation method (P = 0.085), age (P = 0.329) or resection length (P = 0.61). Acetabular chondrolysis was identified in 18 (26%) patients and longer resection length (≥20 cm) showed a trend for risk of acetabular wear (P = 0.132). CONCLUSION: The results of proximal femoral resection and reconstruction with a modular bipolar-type prosthesis were found to be acceptable with infection and local recurrence as short-term complications and loosening and acetabular erosion as long-term complications.

Spatial distribution and determinants of health loss from Kashin-Beck disease in Bin County, Shaanxi Province, China.

BACKGROUND: Kashin-Beck disease (KBD) is one of the major endemic diseases in China, which severely impacts the physical health and life quality of people. A better understanding of the spatial distribution of the health loss from KBD and its influencing factors will help to identify areas and populations at high risk so as to plan for targeted interventions. METHODS: The data of patients with KBD at village-level were collected to estimate and analyze the spatial pattern of health loss from KBD in Bin County, Shaanxi Province. The years lived with disability (YLDs) index was applied as a measure of health loss from KBD. Spatial autocorrelation methodologies, including Global Moran's I and Local Moran's I, were used to describe and map spatial clusters of the health loss. In addition, basic individual information and environmental samples were collected to explore natural and social determinants of the health loss from KBD. RESULTS: The estimation of YLDs showed that patients with KBD of grade II and patients over 50 years old contributed most to the health loss of KBD in Bin County. No significant difference was observed between two genders. The spatial patterns of YLDs and YLD rate of KBD were clustered significantly at both global and local scales. Villages in the southwestern and eastern regions revealed higher health loss, while those in the northern regions exhibited lower health loss. This clustering was found to be significantly related to organically bound Se in soil and poverty rate of KBD patients. CONCLUSIONS: Our results suggest that future treatment and prevention of KBD should focus on endemic areas with high organically bound Se in soil and poor economic conditions. The findings can also provide important information for further exploration of the etiology of KBD.

Bioaccumulation and translocation of trace elements in soil-irrigation water-wheat in arid agricultural areas of Xin Jiang, China.

Pollution resulting from toxic trace elements is an increasing concern around the world especially in developing countries such as China. Rapid industrialisation, urbanisation and agricultural development are the dominant sources of anthropogenic contamination contributed to an increased potential toxicity of trace elements in the irrigation water-soil-food chain. Xin Jiang in China is a reserved cultivated land development area that could provide the most extensive strategic support for food production and arable land security in China. Thus, it is crucial to investigate the bioaccumulation and translocation of trace elements in order to assess the ecological and human health risks in the traditional oasis system of the agricultural areas in Bay Cheng County, Xin Jiang. This study analysed the levels of trace elements in different layers of the soil, the irrigation water and the wheat plants, and the relationships among them. The results indicated that cadmium (Cd) and chromium (Cr) were the primary pollutants in soils and wheats respectively, and they fell into the serious pollution category. However, no trace elements over the pollution limits were detected in irrigation water. The maximum values of trace elements appeared in the soil layers at 5-10 cm and 10-15 cm. The pollution levels of trace elements in the soil layers were found at 0-5 cm and 0-20 cm, which were higher than those at 20-80 cm. In wheat, high amounts of absorption for Se, Cr, Zn and Cu, but low for Pb were detected in different parts of a plant. The roots of wheats were more eco-toxic to Cd, Co and Pb than other tissues, indicating that roots were more effective at absorbing Cd, Co and Pb, as these metals are usually toxic in the soil. Se, Cu and Zn showed a higher ability of being transferred from soils to the edible parts of crops. The bio-transfer factors of Zn, Mo, Cu, Mg and Mn were considerably higher than those of other elements. The average cancer risk of As, Cd, Co, Ni and TCR in wheat grains exceeded the safety reference limit (1 × 10-4). For the exposed population, Cr in wheat was the major contributor to total cancer risk. The average values of HQ of Cr, Mn and As, and total non-cancer risk index exceeded the corresponding effective safe reference doses (HQ > 1).

Santamarine Shows Anti-Photoaging Properties via Inhibition of MAPK/AP-1 and Stimulation of TGF-ß/Smad Signaling in UVA-Irradiated HDFs.

Chronic UVA exposure results in elevated reactive oxygen species in skin which leads to photoaging characterized as upregulated matrix metalloproteinase (MMP)-1 and loss of collagen. Therefore, natural antioxidants are hailed as promising agents to be utilized against photoaging. In the current study, reynosin and santamarine, two known sesquiterpene lactones isolated from Artemisia scoparia, were analyzed for their anti-photoaging properties in UVA-irradiated human dermal fibroblasts (HDFs). Results showed that UVA irradiation (8 J/cm2) upregulated the MMP-1 secretion and expression, and suppressed collagen production, which were significantly reverted by santamarine treatment (10 µM). Although both reynosin and santamarine exhibited ROS scavenging abilities, reynosin failed to significantly diminish UVA-stimulated MMP-1 release. UVA-irradiated HDFs showed increased collagen production when treated with santamarine. As a mechanism to suppress MMP-1, santamarine significantly suppressed the UVA-induced phosphorylation of p38 and JNK and nuclear translocation of p-c-Fos and p-c-Jun. Santamarine promoted collagen I production via relieving the UVA-induced suppression on TGF-ß and its downstream activator Smad2/3 complex. Antioxidant properties of santamarine were also shown to arise from stimulating Nrf2-dependent expression of antioxidant enzymes SOD-1 and HO-1 in UVA-irradiated HDFs. In conclusion, santamarine was found to be a promising natural antioxidant with anti-photoaging properties against UVA-induced damages in HDFs.

Antimalarial diterpenoids from Vitex rotundifolia: Isolation, structure elucidation, and in vitro antiplasmodial activity.

Vitex rotundifolia is an important medicinal plant frequently employed in traditional medicines for the treatment of various ailments. Although this plant species has been under exploration for its constituents by various research groups including our own group, no reports were found regarding the antimalarial potential of this plant or of its purified phytochemicals. Phytochemical investigation of this plant yielded three new (1-3) and five known (4-8) diterpenoids. These compounds were purified by modern chromatographic techniques and their structures were determined by advanced spectroscopic techniques such as nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS). The in vitro antiplasmodial activities were encouraging, as compounds 2, 6, and 8 were found to have significant IC50 values of 1.2, 1.3 and 11.0 µM, respectively against Plasmodium falciparum.

Effect of Quercetin 3-O-ß-D-Galactopyranoside on the Adipogenic and Osteoblastogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stromal Cells.

Natural products, especially phenols, are promising therapeutic agents with beneficial effects against aging-related complications such as osteoporosis. This study aimed to investigate the effect of quercetin 3-O-ß-D-galactopyranoside (Q3G), a glycoside of a common bioactive phytochemical quercetin, on osteogenic and adipogenic differentiation of human bone marrow-derived mesenchymal stromal cells (hBM-MSCs). hBM-MSCs were induced to differentiate into osteoblasts and adipocytes in the presence or absence of Q3G and the differentiation markers were analyzed to observe the effect. Q3G treatment stimulated the osteoblastogenesis markers: cell proliferation, alkaline phosphatase (ALP) activity and extracellular mineralization. In addition, it upregulated the expression of RUNX2 and osteocalcin protein as osteoblastogenesis regulating transcription factors. Moreover, Q3G treatment increased the activation of osteoblastogenesis-related Wnt and bone morphogenetic protein (BMP) signaling displayed as elevated levels of phosphorylated ß-catenin and Smad1/5 in nuclear fractions of osteo-induced hBM-MSCs. The presence of quercetin in adipo-induced hBM-MSC culture inhibited the adipogenic differentiation depicted as suppressed lipid accumulation and expression of adipogenesis markers such as PPARγ, SREBP1c and C/EBPα. In conclusion, Q3G supplementation stimulated osteoblast differentiation and inhibited adipocyte differentiation in hBM-MSCs via Wnt/BMP and PPARγ pathways, respectively. This study provided useful information of the therapeutic potential of Q3G against osteoporosis mediated via regulation of MSC differentiation.

Antiphotoaging Effect of 3,5-Dicaffeoyl-epi-quinic Acid against UVA-Induced Skin Damage by Protecting Human Dermal Fibroblasts In Vitro.

Cutaneous aging is divided into intrinsic and exogenous aging correspondingly contributing to the complex biological phenomenon in skin. Intrinsic aging is also termed chronological aging, which is the accumulation of inevitable changes over time and is largely genetically determined. Superimposed on this intrinsic process, exogenous aging is associated with environmental exposure, mainly to ultraviolet (UV) radiation and more commonly termed as photoaging. UV-induced skin aging induces increased expression of matrix metalloproteinases (MMPs) which in turn causes the collagen degradation. Therefore, MMP inhibitors of natural origin are regarded as a primary approach to prevent or treat photoaging. This study investigated the effects of 3,5-dicaffeoyl-epi-quinic acid (DEQA) on photoaging and elucidated its molecular mechanisms in UVA-irradiated human dermal fibroblasts (HDFs). The results show that treatment with DEQA decreases MMP-1 production and increases type I collagen production in UVA-damaged HDFs. In addition, treatment of UVA-irradiated HDFs with DEQA downregulates MMP-1, MMP-3 and MMP-9 expression via blocking MAPK-cascade-regulated AP-1 transcriptional activity in UVA-irradiated HDFs. Furthermore, DEQA relieves the UVA-mediated suppression of type I procollagen and collagen expression through stimulating TGF-ß/Smad signaling, leading to activation of the Smad 2/3 and Smad 4 nuclear translocation. These results suggest that DEQA could be a potential cosmetic agent for prevention and treatment of skin photoaging.

Syringaresinol Inhibits UVA-Induced MMP-1 Expression by Suppression of MAPK/AP-1 Signaling in HaCaT Keratinocytes and Human Dermal Fibroblasts.

Ultraviolet (UV) irradiation induces detrimental changes in human skin which result in photoaging. UV-induced intracellular changes cause degradation of extracellular matrix (ECM). UV-stimulated cleavage of collagen in ECM occurs via matrix metalloproteinases (MMPs). (±)-syringaresinol (SYR), a phytochemical which belongs to the lignan group of polyphenols, was investigated for its ability to reverse the UVA-induced changes in human HaCaT keratinocytes and dermal fibroblasts (HDFs) in vitro. Effect of SYR on UVA-induced changes was investigated by production and activation of MMPs and its transcriptional upstream effectors; mitogen-activated protein kinases (MAPKs) and pro-inflammatory mediators. Levels of expression were determined using ELISA, RT-PCR and immunoblotting. UVA irradiation stimulated the production of MMP-1 and inhibited collagen production. SYR treatment suppressed MMP-1 and enhanced collagen production in UVA-irradiated HaCaT keratinocytes and HDFs. SYR repressed the UV-induced phosphorylation of p38, ERK and JNK MAPKs in HaCaT keratinocytes while only suppressing JNK phosphorylation in HDFs. In addition, SYR was able to inhibit UVA-induced production of inflammatory cytokines; TNF-α, COX-2, IL-1ß and IL-6. Moreover, SYR suppressed the activator protein-1 (AP-1), a heterodimer of phosphorylated transcription factors c-Jun and c-Fos. SYR-treatment decreased nuclear levels of activated c-Fos and c-Jun as a mechanism to inhibit UVA-induced transcriptional activities leading to MMP-1 production. In conclusion, current results demonstrated that SYR could inhibit UVA-induced upregulation of MMP-1 by suppressing MAPK/AP-1 signaling in HaCaT keratinocytes and HDFs. Therefore, SYR was suggested as a potential compound with antiphotoaging properties against UVA-induced skin aging.