[Synthesis and antifatigue activities of new benzamide derivatives].

To explore novel antifatigue agents targeting with AMPA receptor, 10 compounds were synthesized and their structures were confirmed by 1H NMR, ESI-MS and elemental analysis. 1-BCP was treated as the leading compound. The antifatigue activities were evaluated by weight-loaded forced swimming test, and the AMPA receptor binding affinities were tested with radioligand receptor binding assays. The results unveiled that 5b appeared to possess potent antifatigue activities and high affinity with AMPA receptor, which deserved further studies.

A systematic review of the efficacy and pharmacological profile of Herba Epimedii in osteoporosis therapy.

The purpose of this systematic review is to assess the efficacy and pharmacological profiles of Herba Epimedii in osteoporosis therapy. Four databases were extensively retrieved that include two Chinese electronic databases (VIP Information and CNKI) and two English electronic databases (CA and MEDLINE). Herba Epimedii has been an important traditional herbal medicine for centuries in China and other Asian countries. Recently, quite a few pharmacological effects of Herba Epimedii, its extracts and active components have been identified that include improving bone health and cardiovascular function, regulating hormone level, modulating immunological function, and inhibiting tumor growth. The anti-osteoporosis activity of Herba Epimedii and its extracts have attracted world-wide attention. The literature search has revealed that a lot of studies have recently been carried out related to the bone-strengthening activity of Herba Epimedii and some of its active compounds, such as total flavonoids and icariin. Pharmacokinetic and toxicity studies have confirmed the efficacy and safety of Herba Epimedii and its most abundant active component icariin, while only a few authors have reviewed the anti-osteoporosis properties of the plants. So we summarize the work of various investigators on the effects of Herba Epimedii, its extracts and active components against osteoporosis. The underlying mechanism of osteoprotective action, derivatives of icariin, animal models and cell lines used in the research were also reviewed in this paper.

[Effects of naringin on proliferation, differentiation and maturation of rat calvarial osteoblasts in vitro].

OBJECTIVE: To investigate the effects of naringin on the proliferation, differention and maturaion of rat calvarial osteoblasts (ROB). METHOD: Segregated neonatal SD rat skull, enzyme digestion to obtain ROB. The culture medium was replaced every three days. Serial subcultivation proceeded when cells covered with 80% culture dish. Naringin supplemented into the culture at 1 x 10(-4), 1 x 10(-5), 1 x 10(-6), 1 x 10(-7) mol x L(-1) respectively. MTT method was adopted in proliferation analysis and the activity of ALP was examined after induced 9 days. Search the best concentration and supplemented into the medium, then the osteogenic differentiation markers including the secretion amount of osteocalcin, osteopontin and bone morphogenetic protein-2 were compared between the naringin-supplemented group and the control. Total RNA was isolated and the mRNA level of bFGF, IGF-1, Runx-2, Osterix, ERa and ERbeta was investigated by Real time RT-PCR. Total protein also was isolated and the expression ERa, ERbeta and collagen I was examined by Western blot. After the addition of ICI 182.780, an inhibitor of the estrogen signal pathway, these index also was examined and the changes were compared. RESULT: The ROB proliferation was motivated by naringin dose-dependently. And it evidently leads to osteogenic process and maturation. 1 x 10(-5) mol x L(-1) is the best concentration. Naringin improved the secretion of osteocalcin, osteopontin, bone morphogenetic protein-2 and collagen I significantly. Besides, it can also enhanced the mRNA level of bFGF, IGF-1, Runx-2, Osterix, ERalpha and ERbeta. While all these effects can be restrained by ICI 182.780. CONCLUSION: The naringin with final concentration of 1 x 10(-5) mol x L(-1) enhances the osteogenic differentiation and maturation of ROB significantly, while the promoting effects vanished after the addition of ICI 182.780. These results suggesting that naringin is one of the phytoestrogens and have the activity of bone formation may via estrogen signal pathway, it can be developed into a new drug for osteoporosis therapy.

Mangiferin inhibited neuroinflammation through regulating microglial polarization and suppressing NF-κB, NLRP3 pathway.

Inflammation plays important roles in the progress of neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. Microglia is responsible for the homeostasis of the central nervous system (CNS), and involved in the neuroinflammation. Therefore, it could be potential in treatment of neurodegenerative diseases to suppress the microglia-mediated neuroinflammation. Mangiferin, a major glucoside of xanthone in Anemarrhena Rhizome, has anti-inflammatory, anti-diabetes, and anti-oxidative properties. However, the effect of mangiferin on the inflammatary responses of microglia cells are still poorly understand. In this study, we investigated the mechanism by which mangiferin inhibited inflammation in LPS-induced BV2 microglia cells. BV2 cells were pretreatment with mangiferin followed by LPS stimulation. In vitro assays, NO and cytokines production were quantified. Western blot and immunocytochemistry were used to examine the effect of mangiferin on the polarization of BV2 cells and signaling pathway. The results showed that mangiferin treatment significantly reduced NO, IL-1ß, IL-6 and TNF-α production, also reduced the mRNA and protein of iNOS and COX-2, promoted the polarization of inflammatory toward anti-inflammatory, and inhibited activation of NF-κB and NLRP3 inflammasome. These data suggest that mangiferin has an anti-neuroinflammatory property via regulating microglia macrophage polarization and suppressing NF-κB and NLRP3 signaling pathway, and may act as a potential natural therapeutic candidate for neuroinflammatory diseases.

[Analysis of Industrial VOCs Emission Inventory and Countermeasures in Xiamen].

Based on data from industrial activities and environmental surveys in the six districts of Xiamen, the emission inventory of industrially sourced volatile organic compounds (VOCs) from eight industries in the six districts of Xiamen was calculated for 2019 by applying the emission factor analysis method. The spatial distribution pattern of VOC emission intensity in the six districts of Xiamen was analyzed. VOCs treatment technologies applied in the industries in the VOCs emission inventory were analyzed and countermeasures for improving VOC control were proposed based on the survey of the industries. The results showed that the total VOCs production and VOCs emission from industrial sources in Xiamen was 16027.88 t and 5514.58 t in 2019, respectively. Among them, the VOCs emission from Haicang, Tong'an, Xiang'an, and Jimei districts outside Xiamen Island were 1648.35, 2111.13, 667.52, and 750.48 t, respectively. Fewer VOC emissions from Xiamen Island were observed, which included 292.42 and 44.68 t from Huli and Siming districts, respectively. Except for the Huli District, the spatial distribution of emissions showed a spatial characteristic that the VOCs emission intensities outside Xiamen Island are higher than that of Xiamen Island. Among the eight industries in Xiamen, VOCs emissions were mainly from coating, printing, chemical, and rubber industries, which accounted for 51.21%, 20.18%, 13.63%, and 10.67%, respectively, of the total emissions. The analytic results of the VOCs waste gas disposal technique in Xiamen indicate that, from the perspective of source control, enterprises can effectively control the generation and emission of the VOCs at the source by using low (zero) raw materials. For the terminal disposal procedure, the actual disposal efficiency of UV photolysis/photocatalysis, low-temperature plasma, and biological methods are all lower than 80%, and that of the combined technique of adsorption and catalytic combustion, and the combustion method are both higher than 90%.

Polysaccharide extracted from Portulacae Oleracea L. exerts protective effects against dextran sulfate sodium-induced colitis through inhibition of NF-κB.

Portulacae Oleracea L. (POL) is a traditional Chinese medicine and also an edible vegetable used to treat diarrhea in china for thousands years. Though the therapeutic effect has been proved in clinical trials, the concrete effective component and mechanisms remained elusive. Polysaccharide from POL has been extracted previously and the experiment suggested that POLP could diminish the weight loss and improve the health conditions of mice with DSS induced colitis. Hematoxylin & eosin staining revealed that POLP could improve the histopathological structure of the colon tissue. For the notably variation curve of TNF-α in control, colitis and treatment group, NF-κB was enrolled to investigate the molecular mechanisms of the protective effect of POLP. The protein expression level of NF-κBp65 in cytoplasm increased after POLP treatment of the induced colitis. However, the protein level of NF-κBp65 in the nucleus decreased after administration of POLP. The expression levels of IκBα and NF-κB related proteins Bcl-2 and survivin were also detected and the results suggested that POLP could inhibit the degradation of IκBα and decrease the protein levels of Bcl-2 and Survivin in colitis. It was concluded that POLP could improve the health condition of mice with DSS induced colitis and the mechanisms were closely related with NF-κB via inhibiting the degradation of IκBα.

Radix Dipsaci total saponins stimulate MC3T3-E1 cell differentiation via the bone morphogenetic protein-2/MAPK/Smad-dependent Runx2 pathway.

Radix Dipsaci total saponins (RTS) are primary active components of Radix Dipsaci, which is administered orally for the treatment of osteoporosis according to Chinese Medicine. RTS have also been shown to reduce the risk of bone fractures in rats. However, the detailed molecular mechanisms underlying their action remain elusive. In the present study, the ability of RTS to increase alkaline phosphatase activity, osteocalcin levels and the degree of mineralization was investigated in MC3T3­E1 mouse osteoblast precursor cells. In addition, the associated molecular mechanism was detected. The results revealed that RTS exerted an effect on osteoblastic maturation and differentiation. Induction of differentiation by RTS was associated with an increase in the expression levels of bone morphogenetic protein­2 (BMP­2), phosphorylated (P)­Smad1/5/8, P­ERK1/2, P­p38 and Runt­related transcription factor 2 (Runx2). Blocking BMP­2 expression with noggin significantly reduced the levels of osteoblastic differentiation and subsequently attenuated the expression levels of P­Smad1/5/8, P­ERK1/2, P­p38 and Runx2. This indicated that RTS induced osteoblastic differentiation through BMP­2/mitogen­activated protein kinase/Smad1/5/8­dependent Runx2 signaling pathways and that it may be a promising agent for enhancing bone formation.

Effects of total lignans from Eucommia ulmoides barks prevent bone loss in vivo and in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: The present study systematically investigate the in vivo and in vitro effect of total lignans (TL) extracted from Eucommia ulmoides Oliv. barks on bone formation using ovariectomy rat model and primary cultures of rat osteoblasts. MATERIALS AND METHODS: Eighty 3-month-old female Sprague-Dawley rats were used and randomly assigned into sham-operated group (SHAM) and five ovariectomy (OVX) subgroups, i.e. OVX with vehicle (OVX); OVX with 17α-ethinylestradiol (E2, 25 µg/kg/day); OVX with TL of graded doses (20, 40, or 80 mg/kg/day). The treatment began 4 weeks after the surgery and lasted for 16 weeks. in vitro experiments were performed to determine the potential mechanisms of the anti-osteoporotic effect of TL. RESULTS: Treatment with TL significantly prevent OVX-induced decrease in biomechanical quality of femur such as maximum stress and Young׳s modulus. The mechanical changes were associated with the prevention of a further BMD decrease or even with some improvements in microarchitecture. TL inhibited BMD decrease in the femur caused by OVX, which was accompanied by a significant decrease in skeletal remodeling, as was evidenced by the decreased levels of the bone turnover markers. µCT analysis of the femoral metaphysis showed how to prevent the deterioration of trabecular microarchitecture. TL induced primary osteoblastic cell proliferation and differentiation, inhibition of osteoclastogenesis through an increase in osteoprotegrin (OPG) and a decrease in NF-κB ligand (RANKL) expression in vitro. CONCLUSIONS: We concluded that TL treatment can effectively suppress the loss of bone mass induced by OVX and in vitro evidence suggests this could be through actions on both osteoblasts and osteoclasts.

The importance of the prenyl group in the activities of osthole in enhancing bone formation and inhibiting bone resorption in vitro.

Osteoporosis treatment always aimed at keeping the balance of bone formation and bone resorption. Recently, prenyl group in natural products has been proposed as an active group to enhance the osteogenesis process. Osthole has both the prenyl group and bone-protective activities, but the relationship is still unknown. In this study we found that osthole exerted a potent ability to promote proliferation and osteogenic function of rat bone marrow stromal cells and osteoblasts, including improved cell viability, alkaline phosphatase activity, enhanced secretion of collagen-I, bone morphogenetic protein-2, osteocalcin and osteopontin, stimulated mRNA expression of insulin-like growth factor-1, runt-related transcription factor-2, osterix, OPG (osteoprotegerin), RANKL (receptor activator for nuclear factor-κB ligand), and the ratio of OPG/RANKL, as well as increasing the formation of mineralized nodules. However, 7-methoxycoumarin had no obvious effects. Osthole also inhibited osteoclastic bone resorption to a greater extent than 7-methoxycoumarin, as shown by a lower tartrate-resistant acid phosphatase activity and lower number and smaller area of resorption pits. Our findings demonstrate that osthole could be a potential agent to stimulate bone formation and inhibit bone resorption, and the prenyl group plays an important role in these bone-protective effects.

Antiosteoporosis effect of radix scutellariae extract on density and microstructure of long bones in tail-suspended sprague-dawley rats.

Radix Scutellariae (RS), a medicinal herb, is extensively employed in traditional Chinese medicines and modern herbal prescriptions. Two major flavonoids in RS were known to induce osteoblastic differentiation and inhibit osteoclast differentiation, respectively. This study aimed to investigate the effect of Radix Scutellariae extract (RSE) against bone loss induced by mechanical inactivity or weightlessness. A hindlimb unloading tail-suspended rat model (TS) was established to determine the effect of RSE on bone mineral density and bone microarchitecture. Treatment of RSE at 50 mg/kg/day and alendronate (ALE) at 2 mg/kg/day as positive control for 42 days significantly increased the bone mineral density and mechanical strength compared with TS group. Enhanced bone turnover markers by TS treatment were attenuated by RSE and ALE administration. Deterioration of bone trabecula induced by TS was prevented. Moreover, both treatments counteracted the reduction of bone volume fraction, trabecular thickness and number, and connectivity density. In conclusion, RSE was demonstrated for the first time to prevent osteoporosis induced by TS treatment, which suggests the potential application of RSE in the treatment of disuse-induced osteoporosis.