Effect of turmeric on glycemic status,lipid profile,hs‐CRP,and total antioxidant capacity in hyperlipidemic type 2 diabetes mellitus patients

Diabetes mellitus is the most common metabolic disorder worldwide. This study examined the effect of turmeric supplementation on glycemic status, lipid profile, hs‐CRP and total antioxidant capacity in hyperlipidemic type 2 diabetic patients. In this double‐blind, randomized clinical trial, 80 hyperlipidemic type 2 diabetic patients were divided into turmeric (2,100 mg powdered rhizome of turmeric daily) and placebo groups for 8 weeks. Body weight, fasting plasma glucose, hemoglobin A1c (HbA1c), serum insulin, triglyceride (TG), total cholesterol, low density lypoprotein cholesterol (LDL‐c), high density lypoprotein cholesterol, apolipoprotein A1, apolipoprotein B, high sensitivity C‐reactive protein (hs‐CRP), and total antioxidant capacity were measured before and after intervention. Statistical analysis was carried out using paired and independent t and chi‐square tests. Seventy five patients completed the study. The turmeric group showed significant decreases in body weight, TG, and LDL‐c compared with baseline (p value < 0.05). Body mass index, TG, and total cholesterol decreased significantly in the turmeric group compared with the placebo group (p value < 0.05). No significant changes were observed in other parameters between the two groups after intervention (p value < 0.05). Turmeric improved some fractions of lipid profile and decreased body weight in hyperlipidemic patients with type 2 diabetes. It had no significant effect on glycemic status, hs‐CRP, and total antioxidant capacity in these patients.     

A Novel Extract of Fenugreek Husk (FenuSMART™) Alleviates Postmenopausal Symptoms and Helps to Establish the Hormonal Balance: A Randomized,Double‐Blind,Placebo‐Controlled Study

Despite the widespread use of hormone replacement therapy, various reports on its side effects have generated an increasing interest in the development of safe natural agents for the management of postmenopausal discomforts. The present randomized, double‐blinded, placebo‐controlled study investigated the effect of 90‐day supplementation of a standardized extract of fenugreek (Trigonella foenum‐graecum) (FenuSMART?), at a dose of 1000 mg/day, on plasma estrogens and postmenopausal discomforts. Eighty‐eight women having moderate to severe postmenopausal discomforts and poor quality of life (as evidenced from the scores of Greene Climacteric Scale, short form SF‐36® and structured medical interview) were randomized either to extract‐treated (n = 44) or placebo (n = 44) groups. There was a significant (p < 0.01) increase in plasma estradiol (120%) and improvements on various postmenopausal discomforts and quality of life of the participants in the extract‐treated group, as compared with the baseline and placebo. While 32% of the subjects in the extract group reported no hot flashes after supplementation, the others had a reduction to one to two times per day from the baseline stages of three to five times a day. Further analysis of haematological and biochemical parameters revealed the safety of the extract and its plausible role in the management of lipid profile among menopausal women. Copyright © 2016 John Wiley & Sons, Ltd.     

Coadministration of epigallocatechin‐3‐gallate (EGCG) and caffeine in low dose ameliorates obesity and nonalcoholic fatty liver disease in obese rats

Epigallocatechin‐3‐gallate (EGCG) and caffeine in tea exert anti‐obesity effects and induces nonalcoholic fatty liver disease (NAFLD) amelioration. However, previous studies usually performed a high‐dose EGCG administration, whereas the insecurity was arisen in recent researches. In this study, we treated obese rats with an elaborate dose—40 mg/kg EGCG, 20 mg/kg caffeine, and the coadministration of them as low dose, which were similar to the daily intake; 160 mg/kg EGCG as high dose, which was the maximum safe dose had touched the contentious edge. The results suggested that the coadministration of EGCG and caffeine exerted more remarkable function on suppressing body weight gain, reducing white adipose tissue weight and decreasing the energy intake than single use. This may be due to the variation in serum lipid profile, oxidative stress, and adipose‐derived and inflammatory cytokines. The pathological micrographs showed long‐term high‐fat diets caused severe NAFLD, but it was ameliorated at different levels by all of the administrations. In summary, low dose of EGCG or caffeine only showed a mild effect of anti‐obesity and NAFLD amelioration. The coadministration of them could exert a superior curative effect as well as high dose EGCG but no anxiety regarding safety.     

Anti‐stress Activity of Ocimum sanctum: Possible Effects on Hypothalamic–Pituitary–Adrenal Axis

The present study investigated anti‐stress potential of Ocimum sanctum in chronic variable stress (CVS) paradigm. Further, the possible mechanism of anti‐stress was explored in vitro using cell and cell‐free assays. Rats were administered O. sanctum followed by CVS regimen for a period of 16 days. On days 4, 8, 12, and 16, body weight and immobility time in forced swim test were measured. In addition, the possible inhibitory effect of O. sanctum and ursolic acid on cortisol release and CRHR1 receptor activity were studied in cell‐based assays, while inhibitory effects on 11β‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1) and catechol‐O‐methyltransferase (COMT) were studied in cell‐free assays. CVS group demonstrated less body weight gain and higher immobility time than O. sanctum administered groups, while oral administration of O. sanctum significantly increased body weight gain and decreased the immobility time. Further, O. sanctum and its constituents inhibited cortisol release and exhibited a significant CRHR1 receptor antagonist activity. Also, they had specific inhibitory activity towards 11β‐HSD1 and COMT activity. Thus, O. sanctum was found to be effective in the management of stress effects, and anti‐stress activity could be due to inhibition of cortisol release, blocking CRHR1 receptor, and inhibiting 11β‐HSD1 and COMT activities. Copyright © 2016 John Wiley & Sons, Ltd.     

Lipid‐soluble components of honeybee‐collected pollen exert antiallergic effect by inhibiting IgE‐mediated mast cell activation in vivo

It was shown previously that bee‐collected pollen (bee pollen, BP), inhibited in vitro murine mast cell activation. This study further analysed the antiallergic effect of BP in vivo by measuring cutaneous mast cell activation using a passive cutaneous anaphylaxis reaction. Daily oral administration of BP to mice, dose‐dependently reduced the cutaneous mast cell activation elicited by IgE and specific antigens. Administration of BP also reduced the plasma concentration of malondialdehyde (MDA), an indicator of lipid peroxidation. The inhibitory effect of BP was mostly in a lipid‐ but not in water‐soluble fraction. The HPLC analysis of isoflavones in BP revealed that genistein was a major isoflavone. However, administration of genistein alone at the concentration found in BP, did not show an inhibitory effect as observed in whole BP, suggesting that component(s) other than genistein would be responsible for the inhibitory effect of BP. These results first reveal that lipid‐soluble components of BP exert an antiallergic action by inhibiting the FcåRI‐mediated cutaneous mast cell activation. Copyright © 2009 John Wiley & Sons, Ltd.     

Ficus carica Leaf Extract Modulates the Lipid Profile of Rats Fed with a High‐Fat Diet through an Increase of HDL‐C

Ficus carica has been traditionally used for the treatment of several metabolic syndrome‐related health problems. It was the objective of this study to investigate the preventive effects of a Ficus carica (FC) leaf extract on hyperlipidemia in high fat diet (HFD)‐induced obese male rats. Male Sprague–Dawley rats (180 – 200 g) were fed with a regular diet, HFD or a HFD + oral treatment of either 50 mg/kg or 100 mg/kg of FC or 30 mg/kg pioglitazone for six weeks. A range of parameters was evaluated including body weight development, plasma levels of total cholesterol, triglycerides (TG), low‐density‐lipoprotein cholesterol, high‐density lipoprotein cholesterol (HDL‐C), adiponectin, leptin, glucose, insulin, interleukin‐6 (IL‐6), atherogenic index (AI) and the coronary risk index (CRI). FC significantly lowered TG and IL‐6 levels and elevated HDL cholesterol (p < 0.05). The effects of FC on lipid parameters were more pronounced than those of the positive control pioglitazone. FC significantly lowered AI and CRI (p < 0.01) while it had no effect on adiponectin and leptin levels. Our results demonstrate that preventive treatment with FC significantly improved the lipid profile and decreased adipogenic risk factors in HFD rats most likely mediated through an increase in HDL‐C levels. Copyright © 2013 John Wiley & Sons, Ltd.     

九里香叶对去卵巢大鼠拟雌激素样作用的实验研究

目的探讨九里香叶对去卵巢大鼠的拟雌激素样作用。方法以2%戊巴比妥钠麻醉大鼠,切除大鼠双侧卵巢,对照大鼠切除卵巢旁同样大小的脂肪团。术后7天分组、给药。分为模型组:生理盐水(0.4 mg/kg/d);对照组:生理盐水(0.4 mg/kg/d);戊酸雌二醇组:0.4 m g/kg/d;九里香高剂量组:200 mg/kg/d;九里香中剂量组:100 mg/kg/d;九里香低剂量组:50 mg/kg/d。连续给药90天后,处死大鼠,测定子宫系数。放射免疫法测定血清雌二醇水平。结果给药第30天、60天、90天,与对照组比较,模型组大鼠体质量增幅较大,差异显著;与模型组比较,戊酸雌二醇组、九里香叶高剂量组大鼠体质量增幅较小,差异显著(P0.05)。与模型组比较,戊酸雌二醇组、九里香叶高剂量组大鼠子宫质量和子宫系数明显增加,差异显著(P0.05)。与模型组比较,戊酸雌二醇组、九里香叶高、中、低剂量组大鼠雌二醇明显增加,差异不显著(P0.05)。结论九里香叶具有一定的雌激素样作用。     

Antidyslipidemic Activity of Hot‐water Extracts from Leaves of Cinnamomum osmophloeum Kaneh

The antidyslipidemic activity of hot‐water extracts of Cinnamomum osmophloeum leaves (COE) were evaluated on hamsters fed a high‐fat diet. Oral administration of COE to hyperlipidemic hamsters reduced the total cholesterol (TC), triglyceride (TG) and low‐density lipoprotein (LDL‐C) levels. Compared with hyperlipidemic hamsters, the plasma TC and TG levels of hamsters fed with COE at a dosage of 100 mg/kg body weight for 5 and 10 weeks were significantly reduced to 12.63% and 34.25%, and 33.88% and 36.88%, respectively. Plasma LDL‐C was also reduced to 27.77% after 10 weeks feeding with the same regimen. Standard diagnostic tests indicated that the extracts did not cause damage to hamster liver or kidneys. Based on these results, it is concluded that COE possesses antidyslipidemic activity. The composition of COE was characterized. Two main compounds, kaempferol 3‐O‐β‐d ‐apiofuranosyl‐(1 → 2)‐α‐l ‐arabinofuranosyl‐7‐O‐α‐l ‐rhamnopyranoside (1) and kaempferitrin (2) were identified in the hot‐water extracts. Their contents were 7.56% and 9.95%, respectively. Copyright © 2011 John Wiley & Sons, Ltd.     

Antifertility profile of the aqueous extract of Moringa oleifera roots

An aqueous extract of Moringa oleifera roots was investigated for its estrogenic, anti-estrogenic, progestational and antiprogestational activities. Oral administration of extract progressively increased the uterine wet weight of bilaterally ovariectomized rats. This estrogenic activity was supported by stimulation of uterine histo-architecture. When the extract was given conjointly with estradiol dipropionate (EDP), there was a successive reduction in the uterine wet weight when compared to the gain with EDP alone and uterine histological structures were also inhibited. In the deciduoma test, the highest dose of 600 mg/kg interfered with the formation of deciduoma in 50% of the rats, showing some antiprogestational activity. Doses up to 600 mg/kg of the extract orally failed to induce a decidual response in the traumatized uterus of ovariectomized rats. The antifertility effect of the extract appears to be due to multiple attributes.     

The Phytoestrogenic Compound Cajanol from Pigeonpea Roots is Associated with the Activation of Estrogen Receptor α‐dependent Signaling Pathway in Human Prostate Cancer Cells

In the present study, the main natural estrogen‐agonist/antagonist from Pigeonpea roots was studied by the estrogen receptor α‐dependent signaling pathway in human prostate cancer cell. First, the natural products with estrogenic activity in Pigeonpea roots were screened by pER8‐GFP transgenic Arabidopsis, and cajanol (5‐hydroxy‐3‐(4‐hydroxy‐2‐methoxyphenyl)‐7‐methoxychroman‐4‐one) was confirmed as the active compound. Further study showed that cajanol significantly arrested the cell cycle in the G1 and G2/M phase and induced nuclei condensation, fragmentation and the formation of apoptotic bodies. Western blotting showed that cajanol modulated the ERα‐dependent PI3K pathway and induced the activation of GSK3 and CyclinD1 closely following the profile of PI3K activity. Based on above results, we proposed a mechanism through which cajanol could inhibit survival and proliferation of estrogen‐responsive cells (PC‐3 cells) by interfering with an ERα‐associated PI3K pathway, following a process that could be dependent of the nuclear functions of the ERα. Above all, we conclude that cajanol represents a valuable natural phytoestrogen source and may potentially be applicable in health food industry. Copyright © 2013 John Wiley & Sons, Ltd.     

Antiprotozoal activity of Melampyrum arvense and its metabolites

An activity guided isolation of the H₂O subextract of the crude extract of Melampyrum arvense L. afforded iridoid glucosides: aucubin (1), melampyroside (2), mussaenoside (3), mussaenosidic acid (4), 8‐epi‐loganin (5); flavonoids: apigenin (6), luteolin (7), luteolin 7‐O‐β‐glucopyranoside (8); a lignan glycoside dehydrodiconiferyl alcohol 9‐O‐β‐glucopyranoside (9); and benzoic acid (10). β‐Sitosterol (11) and a fatty acid mixture (12) were identified as the active principles of the CHCl₃ subextract. The structures of the isolates were elucidated by spectroscopic methods, while the composition of 12 was identified by GC‐MS after methylation. Luteolin (7) appeared as the most active compound against Trypanosoma brucei rhodesiense and Leishmania donovani (IC₅₀ values 3.8 and 3.0 μg/mL). Luteolin 7‐O‐β‐glucopyranoside (8) displayed the best antiplasmodial activity against Plasmodium falciparum (IC₅₀ value 2.9 μg/mL). This is the first detailed phytochemical study on Turkish M. arvense and the first report of the antiprotozoal effect of Melampyrum species and its constituents. Copyright © 2010 John Wiley & Sons, Ltd.     

马蹄花提取物对大鼠的抗生育作用(英文)

AIM:To evaluate the anti-fertility effect of methanolic(MeTD) and aqueous(AqTD) flower extracts of Tabernaemon-tana divaricata in rats.METHODS:The anti-fertility activity of the extracts was evaluated using two experimental animal models:1) Estrogenic activity was carried out in immature female rats using ethinyl estradiol as standard.The evaluation parameters includes changes in uterine weight and histopathology of uterus.2) Anti-implantation and early abortifacient activity was performed in female Wistar rats.The number of implants and resorbtions were compared to vehicle control.RESULTS:Phytochemical analysis of MeTD and AqTD revealed the presence of carbohydrates,amino acids,steroids,glycosides,flavonoids,alkaloids and tannins.In estrogenic activity,the MeTD and AqTD were offered significant estrogen-like activity at 500 mg?kg-1,p.o.by increasing the uterine weight com-pared to vehicle control group.In Anti-implantation and early abortifacient activity study,MeTD(500 mg?kg-1,p.o.) showed significant effect and it was evident by decrease in the number of implants and increase in the number of resorbtions compared to vehicle control group.CONCLUSION:The MeTD at 500 mg?kg-1,p.o.possess significant estrogenic,anti-implantation and early abortifacient activ-ity,while the AqTD at 500 mg?kg-1,p.o.was found to possess significant estrogenic activity and the results are in consistent with the literature reports related to anti-fertility effect of flower extracts of Tabernaemontana divaricata.     

Anti‐diabetic and Anti‐hyperlipidemic Effects and Safety of Salacia reticulata and Related Species

Extracts of Salacia reticulata Wight (Hypocrataceae) roots, stems, and leaves have been used in Asia for hundreds of years for the folkloric treatment of diabetes and other health problems. Constituents that have been identified as exhibiting anti‐diabetic effects include salacinol, kotalanol, ponkorinol, salaprinol, and their corresponding de‐0‐sulfonated compounds. Mangiferin, kotalagenin 16‐acetate and various proanthocyanidin oligomers have also been isolated. Studies indicate that Salacia extracts modulate multiple targets that influence carbohydrate and lipid metabolism including α‐glucosidase, aldose reductase, pancreatic lipase, peroxisomal proliferator‐activated receptor‐α, glucose transporter‐4 mediated glucose uptake, and angiotensin II type 1 receptor. Furthermore, Salacia extracts exhibit free radical scavenging, antioxidant and hepatoprotectant activities. In human studies, Salacia extracts have been shown to decrease plasma glucose and insulin levels, decrease HbA1c, and modulate serum lipid levels with no adverse effects being reported. Similar results have been demonstrated in rat and mouse models as well as in vitro systems. Safety of S. reticulata and other Salacia species as S. oblonga and S. chinensis in rats and mice indicate that extracts are exceedingly safe. No clinical studies have examined the effects of Salacia extracts on human weight loss, although weight loss and decreases in weight gain have been demonstrated in animal models. Because of the large number of pharmacologically active compounds, it is difficult to establish standards for extracts. © 2015 The Authors. Phytotheraphy Research published by John Wiley & Sons Ltd.     

Raf and PI3K are the Molecular Targets for the Anti‐metastatic Effect of Luteolin

Metastases are the primary cause of human cancer deaths. Luteolin, a naturally occurring phytochemical, has chemopreventive and/or anticancer properties in several cancer cell lines. However, anti‐metastatic effects of luteolin in vivo and the underlying molecular mechanisms and target(s) remain unknown. Luteolin suppresses matrix metalloproteinase (MMP)‐2 and ‐9 activities and invasion in murine colorectal cancer CT‐26 cells. Western blot and kinase assay data revealed that luteolin inhibited Raf and phosphatidylinositol 3‐kinase (PI3K) activities and subsequently attenuated phosphorylation of MEK and Akt. A pull‐down assay indicated that luteolin non‐competitively bound with ATP to suppress Raf activity and competitively bound with ATP to inhibit PI3K activity. GW5074, a Raf inhibitor, and LY294002, a PI3K inhibitor, inhibited MMP‐2 and ‐9 activities and invasion in CT‐26 cells. An in vivo mouse study showed that oral administration (10 or 50 mg/kg) of luteolin significantly inhibited tumor nodules and tumor volume of lung metastasis induced by intravenous injection of CT‐26 cells. Luteolin also inhibited MMP‐9 expression and activity in CT‐26‐induced mouse lung tissue. These results suggest that luteolin may have considerable potential for development as an anti‐metastatic agent. Copyright © 2012 John Wiley & Sons, Ltd.     

Umbelliferone Improves an Impaired Glucose and Lipid Metabolism in High‐Fat Diet/Streptozotocin‐Induced Type 2 Diabetic Rats

Umbelliferone (UMB) is a natural product that has several pharmacological effects including antihyperglycemic activity in diabetic rats. Thus, the objective of this study was to investigate the effect of UMB on insulin resistance and on the regulation of glucose and lipid metabolism in type 2 diabetic rats. Type 2 diabetes was induced in rats by feeding a high‐fat diet (45 kcal% fat) and a single dose of streptozotocin injection. After 8 weeks of treatment, UMB significantly reduced the elevated blood glucose levels and insulin resistance and increased the liver glycogen and serum adiponectin. Moreover, the serum lipid and the storages of triglyceride and non‐esterified fatty acid in liver tissue were reduced. From histological examination, the lipid droplets in liver tissue were clearly decreased, and the fat cell size in the fat tissue was smaller in diabetic rats treated with UMB. Interestingly, UMB increased fat cell adiponectin, plasma membrane glucose transporter 4 (GLUT4) and peroxisome proliferator‐activated receptor gamma (PPARγ), and liver PPARα protein expressions. Our findings demonstrate that UMB improves glucose and lipid metabolism in type 2 diabetes by stimulating the insulin secretion and the related mechanisms via stimulating expression of adiponectin, GLUT4, PPARγ, and PPARα‐protein expressions. Copyright © 2015 John Wiley & Sons, Ltd.     

The Effects of Low and High Concentrations of Luteolin on Cultured Human Endothelial Cells Under Normal and Glucotoxic Conditions: Involvement of Integrin‐Linked Kinase and Cyclooxygenase‐2

Luteolin protects against high glucose (HG)‐induced endothelial dysfunction whereas its cytotoxicity has been reported against normal endothelial cells. This study was undertaken to determine luteolin cytoprotective and cytotoxic dose ranges and to elucidate their respective mechanisms. Luteolin prevented HG‐induced human umbilical vein endothelial cell (HUVEC) death with an EC50 value of 2.0 ± 0.07 μM. The protective effect of luteolin was associated with decreased intracellular reactive oxygen species (ROS) and Ca²⁺ (Cai²⁺) levels and enhanced nitric oxide (NO) production. At high concentrations, luteolin caused HUVEC death in normal glucose (NG) and HG states (LC₅₀ 40 ± 2.23 and 38 ± 1.12 μM, respectively), as represented by increased ROS and Cai²⁺ and decreased NO. Western blots illustrated that exposure to HG increased cyclooxygenase‐2 (COX‐2) and integrin‐linked kinase (ILK) expression. Luteolin at low concentrations suppressed HG‐mediated up‐regulation of COX‐2 but maintained HG‐induced over‐expression of ILK while at high concentrations significantly increased COX‐2 and decreased ILK expression in both HG and NG states. Our data indicated that cytoprotective action of luteolin was manifested with much lower concentrations, by a factor of approximately 20, compared with cytotoxic activity under both normal or glucotoxic conditions. It appears that luteolin exerts its action, in part, by modulating ILK expression which is associated with regulation of COX‐2 expression and NO production in endothelial cells. Copyright © 2014 John Wiley & Sons, Ltd.     

Lipid‐Lowering Effects of Curcumin in Patients with Metabolic Syndrome: A Randomized,Double‐Blind,Placebo‐Controlled Trial

Human studies of curcumin extract on lipid‐lowering effect have not been completely investigated and have had controversy results. This study tested the effect of daily curcumin extract for 12 weeks on weight, glucose, and lipid profiles in patients with metabolic syndrome. Sixty‐five patients were randomized into two groups; 33 patients taking curcumin extract capsule (630 mg thrice daily) and 32 patients taking a placebo capsule thrice daily for 12 weeks. At 12 weeks after the curcumin extract consumption, the level of high‐density lipoprotein cholesterol (HDL‐C) significantly increased from 40.96 ± 8.59 to 43.76 ± 2.79 mg/dL (p < 0.05), and the level of low‐density lipoprotein cholesterol (LDL) was significantly reduced (120.55 ± 36.81 to 106.51 ± 25.02 mg/dL, p < 0.05). The triglyceride‐lowering effect, a reduction of 65 mg/dL, was also found in this study. In subgroups analysis, the consumption of curcumin may have a lowering cholesterol effect in male patients and an increasing HDL‐C effect in female patients, both of which result in a decrease of T‐Chol/HDL‐C ratio. The intake of the curcumin extract of 1890 mg/day for 12 weeks was associated with lipid‐lowering effect but did not improve weight and glucose homeostasis in the patients with metabolic syndrome. Daily curcumin consumption may be an alternative choice to modify cholesterol‐related parameters, especially in metabolic syndrome patients. Copyright © 2014 John Wiley & Sons, Ltd.     

HIF‐1α/VEGF signaling‐mediated epithelial–mesenchymal transition and angiogenesis is critically involved in anti‐metastasis effect of luteolin in melanoma cells

Tumor metastasis is still the leading cause of melanoma mortality. Luteolin, a natural flavonoid, is found in fruits, vegetables, and medicinal herbs. The pharmacological action and mechanism of luteolin on the metastasis of melanoma remain elusive. In this study, we investigated the effect of luteolin on A375 and B16‐F10 cell viability, migration, invasion, adhesion, and tube formation of human umbilical vein endothelial cells. Epithelial–mesenchymal transition (EMT) markers and pivotal molecules in HIF‐1α/VEGF signaling expression were analysed using western blot assays or quantitative real‐time polymerase chain reaction. Results showed that luteolin inhibits cellular proliferation in A375 and B16‐F10 melanoma cells in a time‐dependent and concentration‐dependent manner. Luteolin significantly inhibited the migratory, invasive, adhesive, and tube‐forming potential of highly metastatic A375 and B16‐F10 melanoma cells or human umbilical vein endothelial cells at sub‐IC₅₀ concentrations, where no significant cytotoxicity was observed. Luteolin effectively suppressed EMT by increased E‐cadherin and decreased N‐cadherin and vimentin expression both in mRNA and protein levels. Further, luteolin exerted its anti‐metastasis activity through decreasing the p‐Akt, HIF‐1α, VEGF‐A, p‐VEGFR‐2, MMP‐2, and MMP‐9 proteins expression. Overall, our findings first time suggests that HIF‐1α/VEGF signaling‐mediated EMT and angiogenesis is critically involved in anti‐metastasis effect of luteolin as a potential therapeutic candidate for melanoma.