Low Doses of Curcuma longa Modulates Cell Migration and Cell–Cell Adhesion

Cell invasion and metastasis are involved in clinical failures in cancer treatment, and both events require the acquisition of a migratory behavior by tumor cells. Curcumin is a promising natural product with anti‐proliferative activity, but its effects on cell migration are still unclear. We evaluated the effects of curcumin on the proliferation, apoptosis, migration, and cell–cell adhesion of keratinocyte, oral squamous cell carcinoma (OSCC), and fibroblast cell lines, as well as in a xenograft model of OSCC. Curcumin (2 μM) decreased cell proliferation in cell lines with mesenchymal characteristics, while cell death was detected only at 50 μM. We observed that highly migratory cells showed a decrease on migration speed and directionality when treated with 2 or 5 μM of curcumin (50% and 40%, respectively, p < 0.05). Using spheroids, we observed that curcumin dose dependently decreased cell–cell adhesion, especially on tumor‐derived spheroids. Also, in a xenograft model with patient‐derived OSCC cells, the administration of curcumin decreased tumor growth and aggressiveness when compared with untreated tumors, indicating the potential antitumor effect in oral cancer. These results suggest that lower doses of curcumin can influence several steps involved in tumorigenesis, including migration properties, suggesting a possible use in cancer therapy. Copyright © 2017 John Wiley & Sons, Ltd.     

Vaccinium angustifolium (lowbush blueberry) leaf extract increases extravillous trophoblast cell migration and invasion in vitro

Perturbations to extravillous trophoblast (EVT) cell migration and invasion are associated with the development of placenta‐mediated diseases. Phytochemicals found in the lowbush blueberry plant (Vaccinium angustifolium) have been shown to influence cell migration and invasion in models of tumorigenesis and noncancerous, healthy cells, however never in EVT cells. We hypothesized that the phenolic compounds present in V. angustifolium leaf extract promote trophoblast migration and invasion. Using the HTR‐8/SVneo human EVT cell line and Boyden chamber assays, the influence of V. angustifolium leaf extract (0 to 2 × 10⁴ ng/ml) on trophoblast cell migration (n = 4) and invasion (n = 4) was determined. Cellular proliferation and viability were assessed using immunoreactivity to Ki67 (n = 3) and trypan blue exclusion assays (n = 3), respectively. At 20 ng/ml, V. angustifolium leaf extract increased HTR‐8/SVneo cell migration and invasion (p < .01) and did not affect cell proliferation or viability. Chlorogenic acid was identified as a major phenolic compound of the leaf extract and the most active compound. Evidence from Western blot analysis (n = 3) suggests that the effects of the leaf extract and chlorogenic acid on trophoblast migration and invasion are mediated through an adenosine monophosphate‐activated protein (AMP) kinase‐dependent mechanism. Further investigations examining the potential therapeutic applications of this natural health product extract and its major chemical compounds in the context of placenta‐mediated diseases are warranted.     

Effects of a Peganum harmala (Zygophyllaceae) preparation for root canal disinfection

The aim of this study was to determine the antimicrobial capacity, minimum inhibitory concentration (MIC), and cytotoxic effects of a Peganum harmala seed extract in comparison to 5.25% sodium hypochlorite (NaOCl). The oral pathogen Enterococcus faecalis was used to evaluate the antimicrobial capacity, and the MIC values were determined through serial dilution. Inhibition zones were measured in millimeter, and the data were analyzed statistically by analysis of variance and the Tukey HSD test. For cytotoxicity testing, P. harmala seed extract and 5.25% NaOCl solution were incubated with L929 fibroblast cells. After 1, 24, and 72 hr of incubation, cells were stained and the optical density determined with an enzyme‐linked immunosorbent assay (ELISA) reader. Data were analyzed with Chi‐Square statistical test. The significance level was set at p < .05. There was no significant difference between the antimicrobial capacity of 5.25% NaOCl and the P. harmala extract (p > .05; MIC 4 μg/ml). The Microculture Tetrazolium (MTT) assay test showed that the cytotoxic effects of the P. harmala extract were significantly lower than 5.25% NaOCl (p < .05). The results show that 5.25% NaOCl and P. harmala seed extract have similar antimicrobial activity against Enterococcus faecalis; but P. harmala, which shows reduced cytotoxicity, should be considered for further investigation as a safe, phytotherapeutic, intracanal irrigant.     

Epoxyazadiradione Purified from the Azadirachta indica Seed Induced Mitochondrial Apoptosis and Inhibition of NFκB Nuclear Translocation in Human Cervical Cancer Cells

Epoxyazadiradione (EAD) is an important limonoid present in Neem (Azadirachta indica) plant. In the present study, we have purified EAD from Neem seed and studied its anticancer potential in human cervical cancer (HeLa) cells. Cell proliferation inhibition studies indicated that the GI₅₀ value of EAD is 7.5 ± 0.0092 μM in HeLa cells, whereas up to 50 μM concentrations EAD did not affect the growth of normal H9C2 cells. The control drug cisplatin inhibited the growth of both HeLa and H9C2 cells with a GI₅₀ value of 2.92 ± 1.192 and 4.22 ± 1.568 μM, respectively. Nuclear DNA fragmentation, cell membrane blebbing, phosphatidylserine translocation, upregulation of Bax, caspase 3 activity and poly (ADP ribose) polymerase cleavage and downregulation of BCl2 in HeLa cells on treatment with EAD indicated the apoptotic cell death. Increase in caspase 9 activity and release of active cytochrome c to the cytoplasm on treatment with EAD confirmed that the apoptosis was mediated through the mitochondrial pathway. Epoxyazadiradione also inhibited the nuclear translocation of nuclear factor κB in HeLa cells. Thus, our studies demonstrated EAD as a potent and safe chemotherapeutic agent when compared with the standard drug cisplatin that is toxic to both cancer and normal cells equally. Copyright © 2017 John Wiley & Sons, Ltd.     

Effect of Water Extracts from Edible Myrtaceae Plants on Uptake of 2‐(n‐(7‐nitrobenz‐2‐oxa‐1,3‐diazol‐4‐yl)amino)‐2‐deoxyglucose in TNF‐α‐Treated FL83B Mouse Hepatocytes

This study investigated the glucose uptake activity of the water extracts from the leaves and fruit of edible Myrtaceae plants, including guava (Psidium guajava Linn.), wax apples [Syzygium samarangense (Blume) Merr. and L.M. Perry], Pu‐Tau [Syzygium jambo (L.) Alston], and Kan‐Shi Pu‐Tau (Syzygium cumini Linn.) in FL83B mouse hepatocytes. The fluorescent dye 2‐(n ‐(7‐nitrobenz‐2‐oxa‐1,3‐diazol‐4‐yl)amino)‐2‐deoxyglucose was used to estimate the uptake ability of the cells. Glucose uptake test showed that pink wax apple fruit extract (PWFE) exhibits the highest glucose uptake activity, at an increment of 21% in the insulin‐resistant FL83B mouse hepatocytes as compared with the TNF‐α‐treated control group. Vescalagin was isolated using column chromatography of PWFE. This compound, at the concentration of 6.25 µg/mL, exhibits the same glucose uptake improvement in insulin‐resistant cells as PWFE at a 100‐µg/mL dose. We postulate that vescalagin is an active component in PWFE that may alleviate the insulin resistance in mouse hepatocytes. Copyright © 2012 John Wiley & Sons, Ltd.     

Effects of Tilianin on Proliferation,Migration and TGF‐β/Smad Signaling in Rat Vascular Smooth Muscle Cells Induced with Angiotensin II

Flavonoid Tilianin was isolated from Dracocephalum moldavica, and its pharmacological mechanism on proliferation, migration and the TGF‐β/Smad signaling pathway in rat vascular smooth muscle cells (VSMCs) induced with Angiotensin II (Ang II) was systematically evaluated. Primary rat VSMCs were stimulated with Ang II to induce proliferation. The cells were then treated with Tilianin for 24 or 48 h. MTT assay and Transwell assays were used to evaluate the effects of Tilianin on proliferation and migration. The expression of intracellular proliferating cell nuclear antigen (PCNA), intercellular adhesion molecule‐1 (ICAM‐1) and vascular cell adhesion molecule‐1 (VCAM‐1) were measured by immunohistochemistry as verification of effects on proliferation and migration. The expression of TGF‐β1, Smad2 and Smad3 mRNA was measured by qRT‐PCR, and the expression of TGF‐β1 and P‐Smad2/3 protein was measured by Western blotting. The results show that Tilianin can inhibit proliferation and expression of intracellular PCNA in VSMCs induced with Ang II, in a dose‐dependent manner. Tilianin also mediates a dose‐dependent inhibition of migration and the expression of intracellular ICAM‐1, VCAM‐1, MMP‐2 and MMP‐9. Furthermore, TGF‐β1, Smad2, Smad3, Smad2/3 and P‐Smad2/3 in Ang II‐induced VSMCs are suppressed by Tilianin. The inhibitory effects of Tilianin support its use in the suppression and treatment of atherosclerosis. Copyright © 2017 John Wiley & Sons, Ltd.     

健脾补肾活血方对大鼠骨髓源内皮祖细胞生物学功能的影响

目的:探讨健脾补肾活血方对大鼠骨髓源内皮祖细胞增殖、迁移及黏附的影响。方法:体外分离培养大鼠骨髓源内皮祖细胞,设空白对照组、健脾补肾活血方低剂量组(0.35 g/ml)、健脾补肾活血方中剂量组(0.65 g/ml)、健脾补肾活血方高剂量组(1.0 g/ml)。药物干预24 h后,MTT法检测细胞增殖水平,Transwell检测细胞迁移能力,黏附实验检测细胞黏附能力。结果:与空白对照组比较,不同浓度的健脾补肾活血方以剂量依赖方式显著提高大鼠骨髓源内皮祖细胞的增殖水平,促进细胞迁移,增强细胞的黏附能力,且健脾补肾活血方高剂量组对细胞增殖、迁移及黏附的影响最大。结论:健脾补肾活血方能促进大鼠骨髓源内皮祖细胞的增殖、迁移及黏附功能,具有恢复细胞生物学功能的作用。     

A chemically characterized ethanolic extract of Thai Perilla frutescens (L.) Britton fruits (nutlets) reduces oxidative stress and lipid peroxidation in human hepatoma (HuH7) cells

Perilla frutescens is cultivated in East Asian countries including Thailand, and the nutlets (single‐seeded fruits) are used as traditional and medicinal food. Perilla nutlets extracted by ethyl acetate (EA), 80% ethanol (Eth), and hot water (HW) sequentially were chemically characterized using high‐resolution accurate liquid chromatography‐mass spectrometry with the main compounds detected assigned as rosmarinic acid and derivatives of the flavones apigenin and luteolin, with the more diverse chemical composition observed with the Eth extract. All extracts showed dose‐dependent free‐radical scavenging activity, with the Eth extract the most potent (IC₅₀ = 3.43 mg/ml for ABTS^? scavenging and 0.27 mg/ml for DPPH^? scavenging). The Eth extract also inhibited AAPH‐induced hemolysis (IC₅₀ = 0.07 mg/ml) more potently than did the HW (IC₅₀ = 0.38 mg/ml) and EA extracts (IC₅₀ = 1.63 mg/ml). An MTT test revealed all the extracts were noncytotoxic at concentrations up to 200 μg/ml. Only the Eth and EA extracts showed protective effects against the generation of reactive oxygen species and lipid peroxidation in FeCl₃‐induced HuH7 cells in a dose‐dependent manner. Our findings suggest the Eth extract of Thai perilla nutlets, containing rosmarinic acid and flavones and their derivatives, may have potential to provide protection against oxidative stress in hepatic disorders.     

The chondroprotective effect of diosmin on human articular chondrocytes under oxidative stress

Excessive oxidative stress, which can amplify inflammatory responses, is involved in the pathologic progression of knee osteoarthritis. Diosmin is known to possess a variety of biological functions such as antiinflammatory and antioxidant activities. We therefore demonstrated the chondroprotective potentials of diosmin on human articular chondrocytes under oxidative stress. The cytotoxicity of diosmin (5, 10, 50, and 100 μM) to chondrocytes was first evaluated. Subsequently, the cells were treated with diosmin (5 and 10 μM) after hydrogen peroxide (H₂O₂) exposure. We found that the cytotoxicity of diosmin occurred in a dose‐dependent manner (10, 50, and 100 μM), and low‐dose diosmin (5 μM) slightly impaired cell viability. Diosmin supplementations (5 and 10 μM) did not show beneficial effects on mitochondrial activity, cytotoxicity, proliferation, and survival and the cell senescence was ameliorated in H₂O₂‐exposed chondrocytes. On the other hand, diosmin down‐regulated the mRNA levels of iNOS, COX‐2, IL‐1β, COL1A1, MMP‐3, and MMP‐9; up‐regulated TIMP‐1 and SOX9; and improved COL2A1 in chondrocytes under oxidative stresses. Furthermore, diosmin also regulated glutathione reductase and glutathione peroxidase of H₂O₂‐exposed chondrocytes. In conclusion, diosmin displayed a remarkable antiinflammatory effect compared with the antioxidant capacity on human chondrocytes. Diosmin can maintain the homeostasis of extracellular matrix of articular cartilage.     

番石榴叶新颖杂萜醛类波谱学特征

新奇杂萜醛类化合物独存在番石榴叶中,论文归纳其波谱学特征与生源途径,对文献波谱数据进行综合整理分析。综述结果表明杂萜醛类波谱学特征鲜明,文献杂萜醛位序编号不一致,具有合理生源途径,是番石榴叶的特征化学成分。     

Determination of the wound healing effect of Calendula extracts using the scratch assay with 3T3 fibroblasts

Pharmacological relevance

Presentation of the scratch assay as a convenient and inexpensive in vitro tool to gain first insights in the wound healing potential of plant extracts and natural compounds.

Aim of the study

The present study deals with the optimization of the scratch assay which can be used as an in vitro model for quantification of fibroblast migration to and proliferation into the wounded area. It is suitable for the first evaluation of the wound re-epithelialization potential of crude herbal extracts, isolated compounds and pharmaceutical preparations. As a proof of concept three preparations from traditional medicinal plants were investigated.

Materials and methods

Swiss 3T3 albino mouse fibroblasts were used in monolayers and platelet derived growth factor as positive control. Hexane and ethanolic extracts from Calendula officinalis and Matricaria recutita, Hypericum oil as well as the triterpenoids faradiol myristate and palmitate were studied. To differentiate between proliferation and migration antimitotic mitomycin C was added.

Results

Both extracts of Calendula officinalis stimulated proliferation and migration of fibroblasts at low concentrations, e.g. 10 μg/ml enhanced cell numbers by 64.35% and 70.53%, respectively. Inhibition of proliferation showed that this effect is mainly due to stimulation of migration. Faradiol myristate and palmitate gave comparable stimulation rates at an almost 50 μg/ml concentration, indicating that they contribute partially, but not most significantly to the wound healing effects of Calendula preparations. Extracts from Matricaria recutita were only moderately active. Hypericum oil was cytotoxic at concentrations higher than 0.5 μg/ml.

Conclusions

The scratch assay in the present form can be used as a promising scientific approach and platform to differentiate between plant extracts known for their wound healing and their anti-inflammatory properties.     

Inhibitory and inductive effects of Corydalis saxicola Bunting total alkaloids (CSBTA) on cytochrome P450s in rats

Corydalis saxicola Bunting, a well‐known traditional Chinese medicine in south China, has been widely used for the treatment of various hepatic diseases. Its active ingredients are Corydalis saxicola Bunting total alkaloids (CSBTA), which primarily include dehydrocavidine, palmatine, and berberine. These representative alkaloids could be metabolized by hepatic CYP450s. Hence, it is necessary to investigate the potential influences of CSBTA on CYP450s to explore the possibility of herb–drug interactions. In present study, in vitro inhibition and in vivo induction studies were performed to evaluate the potential effects of CSBTA extract on CYP450s in rats. Inhibition assay illustrated that CSBTA exerted inhibitory effects on CYP1A2 (IC₅₀, 38.08 μg/ml; K_i, 14.3 μg/ml), CYP2D1 (IC₅₀, 20.89 μg/ml; K_i, 9.34 μg/ml), CYP2C6/11 (IC₅₀ for diclofenac and S‐mephenytoin, 56.98 and 31.59 μg/ml; K_i, 39.0 and 23.8 μg/ml), and CYP2B1 (IC₅₀, 48.49 μg/ml; K_i, 36.3 μg/ml) in a noncompetitive manner. Induction study showed CSBTA had obvious inhibitory rather than inductive effects on CYP1A2 and CYP2C6/11. Interestingly, neither inhibition nor induction on CYP3A was observed for CSBTA. In conclusion, CSBTA–drug interactions might occur through CYP450s inhibition, particularly CYP1A and CYP2D. Further studies are still needed to elucidate the underlying mechanisms of inhibition.     

山豆根对小鼠黑色素瘤细胞B16-BL6生长、增殖的影响

目的研究山豆根对小鼠黑色素瘤细胞B16-BL6生长、增殖的影响。方法培养小鼠黑色素瘤细胞B16-BL6并随机分为对照组和处理组,对照组用不含药物的RMPI1640培养基进行处理,处理组分别采用含有400μg/ml、500μg/ml、600μg/ml、700μg/ml、800μg/ml山豆根提取物的RMPI1640培养基进行处理。采用细胞增殖抑制实验、黏附实验、侵袭重组基底膜实验、趋化性运动实验观察山豆根提取物对黑色素瘤细胞B16-BL6增殖、黏附、侵袭和转移的影响。结果山豆根提取物终浓度为700、800μg/ml时,B16-BL6细胞增殖生长OD值明显低于对照组(t=2.526,4.371,P0.05);山豆根提取物终浓度为500、600、700、800μg/ml时,黏附能力OD值明显低于对照组(t=4.856,8.515,8.926,12.357,P0.05),侵袭细胞数明显低于对照组(t=4.661,9.824,12.460,16.300,P0.05),趋化性运动细胞数明显低于对照组(t=2.698,3.906,6.012,7.974,P0.05)。结论山豆根具有抑制小鼠黑色素瘤细胞B16-BL6增殖、黏附、侵袭和转移的能力,且与药物剂量呈依赖性关系。     

寿胎丸含药血清对人早孕滋养层细胞增殖、侵袭、迁移能力的影响

  目的：探讨寿胎丸含药血清对人早孕滋养层细胞增殖、侵袭、迁移能力的调节作用。  方法：体外分离培养人早孕滋养层细胞,采用高、中、低剂量寿胎丸含药血清进行干预,以空白血清、地屈孕酮含药血清为对照。采用噻唑蓝(MTT)比色法、流式细胞术(FCM)及Transwell 侵袭移动实验测定滋养层细胞的增殖活性、周期分布及侵袭迁移能力。  结果：与空白组比较,滋养层细胞经寿胎丸含药血清干预后,细胞的增殖活性、侵袭迁移能力明显增强,S期细胞比例增高,G2/M期细胞比例降低(P<0.05)。与寿胎丸低剂量组比较,寿胎丸中、高剂量组滋养层细胞的增殖活性、侵袭迁移能力明显增强,细胞周期分布变化更加明显(P<0.05)。  结论：寿胎丸含药血清可促进人早孕滋养层细胞的增殖活性及侵袭迁移能力,减少细胞凋亡。     

In vitro antiprotozoan activity and mechanisms of action of selected Ghanaian medicinal plants against Trypanosoma,Leishmania, and Plasmodium parasites

Trypanosomiasis, leishmaniasis, and malaria are protozoan infections of public health importance with thousands of new cases recorded annually. Control of these infection(s) with existing chemotherapy is limited by drug toxicity, lengthy parenteral treatment, affordability, and/or the emergence of resistant strains. Medicinal plants on the other hand are used in the treatment of various infectious diseases although their chemical properties are not fully evaluated. In this study, we screened 112 crude extracts from 72 selected Ghanaian medicinal plants for anti‐Trypanosoma, anti‐Leishmania, and anti‐Plasmodium activities in vitro and investigated their mechanisms of action. Twenty‐three extracts from 20 plants showed significant antiprotozoan activity against at least 1 of 3 protozoan parasites screened with IC₅₀ values less than 20 μg/ml. Eleven extracts showed high anti‐Trypanosoma activity with Bidens pilosa whole plant and Morinda lucida leaf extracts recording the highest activities. Their IC₅₀ (selectivity index [SI]) values were 5.51 μg/ml (35.00) and 5.96 μg/ml (13.09), respectively. Nine extracts had high anti‐Leishmania activity with Annona senegalensis and Cassia alata leaf extracts as the most active. Their IC₅₀ (SI) values were 10.8 μg/ml (1.50) and 10.1 μg/ml (0.37), respectively. Six extracts had high anti‐Plasmodium activity with the leaf and stem‐bark extracts of Terminalia ivorensis recording the highest activity. Their IC₅₀ (SI) values were 7.26 μg/ml (129.36) and 17.45 μg/ml (17.17), respectively. Only M. lucida at 25 μg/ml induced significant apoptosis‐like cell death in Trypanosoma parasites. Anti‐Leishmania active extracts induced varying morphological changes in Leishmania parasites such as multiple nuclei and/or kinetoplast, incomplete flagella division, or nuclear fragmentation. Active extracts may be potential sources for developing new chemotherapy against these infections.     

Effects of Nigella sativa fixed oil on blood homeostasis in rat.

We investigated the effects of the fixed oil of Nigella sativa seeds in rats by monitoring blood homeostasis and body weight as well as toxicity. Animals were treated daily with an oral dose of 1 ml/kg body weight of the N. sativa seed fixed oil for 12 weeks. Changes in key hepatic enzymes levels were not observed in N. sativa treated rats after 12 weeks of treatment. The serum cholesterol, triglycerides and glucose levels and the count of leukocytes and platelets decreased significantly by 15.5, 22, 16.5, 35 and 32%, compared to control values, respectively; while haematocrit and haemoglobin levels increased significantly by 6.4 and 17.4%, respectively. In parallel, significant slowdown of the body weight evolution was observed in N. sativa treated animals comparatively to the animal control group. On the other hand, no mortality was noted for ten times the therapeutic dose in mice, during 15 days period after the oil administration (10 ml/kg p.o.). These results support the traditional use of N. sativa seeds as a treatment of the dyslipidemia and the hyperglycaemia, and related abnormalities; however, indicate a relative toxicity of this plant. Acute and chronic toxicity, and the mode of the action of the N. sativa fixed oil must be studied.     

Quercetin reduces TNF‐α‐induced mesangial cell proliferation and inhibits PTX3 production: Involvement of NF‐κB signaling pathway

Lupus nephritis (LN) is an autoimmune disease caused by systemic lupus erythematosus. Excessive proliferation of mesangial cells is one of the most serious pathological manifestations of LN. In addition, the expression of PTX3 is elevated in the serum of patients with LN. Quercetin has good anti‐inflammatory effects and immunomodulatory activities. In this study, the result of MTT indicated that quercetin treatment alleviated the excessive proliferation of mesangial cells. ELISA and immunofluorescence experiments showed that quercetin treatment inhibited the expression of PTX3. Three doses of quercetin (20, 40, and 80 μM) were selected for the experiment. It is noteworthy that the efficacy of quercetin at 80 μM was significantly better than that of other dose groups. And the effect in inhibiting PTX3 expression was comparable with that of the PDTC (80 μM) positive control. Western blot and qRT‐PCR analysis revealed that quercetin treatment reduced the expression of nuclear factor‐κB p65 and IKKβ, increased the expression of IκBα, and inhibited the expression of PTX3. In conclusion, through inhibiting the activation of nuclear factor‐κB signaling pathway, quercetin treatment could reduce the expression of PTX3 and inhibit the excessive proliferation of mesangial cells, suggesting that quercetin is a potential therapeutic drug for LN.     

Celastrol inhibits growth and metastasis of human gastric cancer cell MKN45 by down‐regulating microRNA‐21

Celastrol could inhibit cancer cell growth in vitro. However, effect(s) of celastrol on gastric cancer is not well studied. Therefore, we investigated the effects of celastrol on human gastric cancer cell line MKN45 and the underlying mechanisms. We found that celastrol inhibited cell proliferation, migration, and invasion and induced cell apoptosis and G2/M cell cycle arrest (p < .05, p < .01, or p < .001). Under celastrol treatment, overexpression of microRNA‐21 (miR‐21) increased cell viability, migration, and invasion and inhibited cell apoptosis compared with negative control (p < .05, p < .01, or p < .001). In addition, the phosphorylation of PTEN was significantly up‐regulated, whereas PI3K, AKT, p65, and IκBα phosphorylation was statistically decreased by celastrol (p < .05 or p < .01) and then further reversed by miR‐21 overexpression (p < .05 or p < .01). On the other side, miR‐21 silence showed contrary results (p < .05) as relative to miR‐21 overexpression. In conclusion, celastrol inhibits proliferation, migration, and invasion and inactivates PTEN/PI3K/AKT and nuclear factor κB signaling pathways in MKN45 cells by down‐regulating miR‐21.     

Investigations on the antinociceptive effect of Psidium guajava leaf essential oil and its major constituents

The antinociceptive effect of leaf essential oil from Psidium guajava and its major constituents, β-caryophyllene and α-pinene was assessed using chemical (formalin and acetic acid) and thermal (hot-plate) nociceptive tests in adult male albino mice. Oral administration of 100, 200 and 400 mg/kg of essential oil produced a significant antinociceptive effect in the formalin test and at 200 and 400 mg/kg in the acetic acid- induced writhing test. Of the major components only α-pinene, but not the β-caryophyllene, demonstrated significant antinociception in the formalin test. Neither the essential oil nor the major components could exert any significant effect in the hot-plate test. Pretreatment of mice with caffeine (20 mg/kg, i.p.), significantly inhibited the antinociceptive effect of essential oil in the formalin test. Naloxone (1 mg/kg, s.c.), the opioid antagonist, however, failed to antagonize it. These results suggest that the antinociceptive effect of P. guajava essential oil is probably mediated by endogenously released adenosine. © 1998 John Wiley & Sons, Ltd.     

Apigenin inhibits growth of the Plasmodium berghei and disrupts some metabolic pathways in mice

Due to the challenges in the control, prevention, and eradication of parasitic diseases like malaria, there is an urgent need to discover new therapeutic agents. Plant‐derived medicines may open new ways in the field of antiplasmodial therapy. This study is aimed to investigate the toxicity and in vivo antiplasmodial activity of apigenin, a dietary flavonoid. Apigenin cytotoxicity was investigated on Huh7 cell line, brine shrimp (Artemia salina) larva, and human red blood cells. In vivo toxicity of apigenin was assessed by metabolomics approaches. Apigenin exhibited significant suppression of parasitemia in a dose‐dependent manner; it suppressed Plasmodium berghei growth by 69.74%, 50.3%, and 49.23% at concentrations of 70, 35, and 15 mg/kg/day, respectively. The IC₅₀ value for apigenin after 24 hr exposure to Huh7 cells was 225 μg/ml. Apigenin did not show noticeable toxicity on A. salina and also on the membrane integrity of red blood cells. After 24 hr exposure of mice to apigenin, alterations were seen in the metabolism of glucocorticoids and mineralocorticoids, bile acid metabolism (alternative pathway), sulfur metabolism, bile acid metabolism, metabolism of estrogens and androgens, cholesterol catabolism, and biosynthesis of cholesterol. These findings indicate that apigenin has potential in vivo antiplasmodial activity against P. berghei infected mice with high selectivity against malaria, but it can disrupt some metabolic pathways in mice.