Type-1 diabetes: Lessons from a decade of preclinical studies on phytotherapy.

BACKGROUND: In recent decades, numerous herbal products have been shown to have antihyperglycemic and beta cell-regenerative effects in animal studies. However, there is no clinical evidence that those products completely cure patients with type-1 diabetes (T1D). Therefore, it seems that most of the phytochemicals do not have a significant impact on human beta cells, and the results of experimental studies conducted on them may not be generalizable to the clinic. PURPOSE: The present work aims to review extensively the methods and results of preclinical studies on phytotherapy of T1D published in the last 10 years. METHODS: This paper critically analyzes the designs of studies, treatment protocols, methods of diabetes induction, characteristics of the studied animals, clinical relevance, reproducibility of research, and other aspects related to conducting preclinical studies on T1D. We discussed limitations that make many of the results of these studies not generalizable to the clinic. Finally, some recommendations were given to improve studies on the phytotherapy of T1D to avoid misleading interpretations about the antidiabetic effect of herbal compounds. CONCLUSION: This paper can be considered a practical guide for researchers interested in the field of phytotherapy of T1D to increase the reliability, reproducibility, and validity of their preclinical studies.

Pro-apoptotic effect of chloroform fraction of Moraea sisyrinchium bulb against glioblastoma cells.

INTRODUCTION: Glioblastoma is a common malignant brain tumor, with limited therapeutic options. In our previous study, the Moraea sisyrinchium plant showed cytotoxicity against glioblastoma and hepatocellular carcinoma cells. Among different parts of this plant (flower, stem, and bulb), the bulb showed better anticancer potential. The present work aimed to test the anticancer activity of different fractions of the bulb extract, to determine its phytochemicals, and to study its mechanism action on glioblastoma. METHODS: The bulb extract was partitioned into different fractions using immiscible solvents. The U87 glioblastoma cells were incubated with the obtained fractions. Then, the cell proliferation assay (MTT), cell migration test (scratch), cell cycle analysis (propidium iodide staining), apoptosis/necrosis assay (annexin V/propidium iodide staining), and real-time PCR (PTEN, Akt, mTOR, BAX and BCL-2 genes) were performed. Phytochemicals were determined using liquid chromatography-mass spectroscopy. RESULTS: The chloroform fraction showed more antiproliferative effect than n-hexane, ethyl acetate, and n-butanol fractions. Also, chloroform fraction induced cell cycle arrest, increased apoptosis, and inhibited cell migration ability (P < 0.05). The expression of PTEN, mTOR, and BAX genes was significantly up-regulated, while the expression of Akt and Bcl-2 showed down-regulation. The phytochemicals identified in the chloroform fraction were mainly xanthones, phytosterols, and isoflavones. CONCLUSION: The chloroform fraction of Moraea sisyrinchium bulb inhibits the proliferation and migration of glioblastoma cells by inducing cell cycle arrest and apoptosis by upregulation of the PTEN gene and Bax/Bcl-2 ratio. The identified compounds in the chloroform fraction are potential candidates for further investigation as anticancer agents against glioblastoma.

Evaluation of acute, subacute, and subchronic toxicity of a hepatoprotective herbal formulation.

Background: The possible toxicity of natural products must be tested before being used in the market. The present work aimed to evaluate acute, subacute, and subchronic toxicity of an herbal formulation containing Anethum graveolens, Cynara scolymus, Citrus aurantium, Portulaca oleracea, and Silybum marianum. Material and methods: Acute toxicity (2000 mg/kg, single dose) and sub-acute toxicity (600 and 1200 mg/kg/day, 4 weeks) tests were performed on female and male rats according to OECD 423 and OECD 407 guidelines, respectively. In the subchronic study (12 weeks), the animals were divided into three groups (6 females and 6 males per group): control, low-dose group (food supplemented with 300 mg/kg of the herbal product), and high-dose group (600 mg/kg). Results: The herbal product at a single dose of 2000 mg/kg did not induce mortality for 14 days. In the sub-acute study, administration of the product for 28 days at 1200 mg/kg/day had no effect on survival, appetite (water and food consumption), body weight, serum biochemical parameters (BUN, creatinine, AST, ALT, ALP, bilirubin, albumin), histology of vital organs (liver, kidney, heart, brain), and hematological markers related to erythrocyte, platelet, and leukocyte. Similarly, in the subchronic study, the product did not induce mortality, change in histology of the vital organs, or alteration in hematological or biochemical parameters (except for an increase in ALP in female rats received 600 mg/kg). Conclusion: The formulated product shows no signs of toxicity in rats up to 2000 mg/kg, 1200 mg/kg, and 600 mg/kg in acute, subacute, and subchronic phases, respectively. It is suggested to monitor ALP levels in females in case of long-term use of the product.

The antihyperglycemic and hypolipidemic effects of Ribes khorassanicum hydro-ethanolic extract co-administration in type 2 diabetic patients: A randomized double blind placebo controlled trial.

Objective: The present randomized clinical trial assessed the antihyperglycemic and hypolipidemic effects of hydro-ethanolic extract of Ribes khorassanicum. Materials and Methods: Eighty type 2 diabetic patients were randomly allocated to placebo or intervention groups and respectively received placebo or extract capsules (700 mg, bid) beside their conventional medication for 3 months. Patients' blood pressure and blood levels of fasting blood glucose (FBS), glycosylated hemoglobin (HbA1c), 2 hr postprandial glucose (2hPPG), triglyceride, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured at the beginning of the study and after 3 months of treatment. For determination of plant safety, liver enzymes (SGOT and SGPT) and kidney function (in terms of urea, creatinine, and microalbumin levels) were assessed and patients were asked to report adverse effects. Results: The R. khorasanicum hydro-ethanolic extract supplementation significantly decreased the levels of FBS, total cholesterol, triglyceride, and LDL-C in the extract group compared to the placebo group (p<0.05-p<0.01). However, 2hPPG, HbA1c, HDL-C, SGOT, SGPT, urea, creatinine, and urine microalbumin values were not significantly different between the placebo and the extract groups. No adverse effects were reported by the patients. Conclusion: Co-supplementation of diabetic patients with R. khorasanicum extract ameliorated hyperglycemia and hyperlipidemia without causing any adverse effects; therefore, the plant extract may be recommended as a complementary therapy to improve diabetes-induced metabolic disturbances.

Efficacy of an herbal compound in decreasing steatosis and transaminase activities in non-alcoholic fatty liver disease: A randomized clinical trial

Abstract Hepatoprotective effects of many herbal agents have been reported in animal studies and clinical trials. In this study, five hepatoprotective plants with potent antioxidant, anti-inflammatory, and hypolipidemic effects were chosen to prepare a polyherbal compound for managing NAFLD. Sixty patients with NAFLD were randomly divided into treatment and control groups (2:1 ratio). Both group were advised to take healthy diet and exercise. The treatment group also received herbal capsules containing 400 mg of the mixture of Anethum graveolens, Citrus aurantium, Cynara scolymus, Portulaca oleracea, and Silybum marianum (2 capsules, thrice daily, for two months). The liver ultrasound and biochemical markers including the serum lipids, liver enzymes, and glucose were evaluated before starting the study and at the end of the treatment. Thirty patients in the treatment group and sixteen patients in the control group completed the study. The herbal compound significantly decreased the serum level of alanine transaminase (ALT), aspartate transaminase (AST), and total cholesterol. Treatment with the herbal compound significantly improved the grade of the fatty liver, but no significant change was found in the control group. In conclusion, the formulated herbal compound appeared to be effective in biochemical improvement and decreasing the grade of the fatty liver in the patients with NAFLD.

Protective Effects of Morus nigra and Its Phytochemicals against Hepatotoxicity: A Review of Preclinical Studies.

BACKGROUND: Our liver has a variety of vital functions including removing poisons, storing energy, immunological roles, and secretory and excretory functions. It may face some kinds of diseases caused by viruses, hepatotoxic chemicals, drugs, alcohol, and inherited disorders. Oxidative stress and inflammation are in the core of mechanisms of liver damages induced by viruses or chemical agents. SUMMARY: Morus nigra (M. nigra), generally known as black mulberry, exhibited wide-spectrum pharmacological effects including antidiabetic, antinociceptive, anticancer, and hepatoprotective activities. Different parts of this plant particularly the fruit and leaf have shown beneficial effects on hepatocytes in cell culture and animal models of liver damages induced by chemicals (e.g., CCl4), drugs (e.g., paracetamol), diet (e.g., high fat), diabetes, etc. The beneficial effects of M. nigra on the liver are attributed to the presence of considerable amounts of phenolic compounds such as anthocyanins, flavonols, and phenolic acids. The present review is aimed to focus on the hepatoprotective activities of M. nigra and its phytochemicals and the mechanisms responsible for these activities. Key Messages: The evidence reviewed in this study can help design clinical trials on M. nigra in patients with liver disorders and develop a hepatoprotective herbal medicine.

Morus nigra L. extract prolongs survival of rats with hepatocellular carcinoma.

Morus nigra is a rich source of anthocyanins, phytochemicals that have anticancer effects. This study aimed to investigate the effects of M. nigra extract (MNE) on diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC). Male Sprague-Dawley rats were assigned into four groups (n = 10): control, DEN, and DEN +100 or 400 mg/kg of MNE. After 4 months, the DEN group showed a significant mortality rate, hepatic lipid peroxidation, dysplastic nodules in the cirrhotic liver, and an increase of blood bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). Also, the body weight gain, blood albumin and glucose, liver antioxidant capacity (thiol groups), and some hematological parameters (RBC, hematocrit, hemoglobin, and platelet) were significantly decreased in the DEN group. MNE significantly increased survival, reduced the size of HCC nodules, improved liver oxidant/antioxidant status, and prevented the above-mentioned changes in the blood (except ALP, glucose, and platelet). Quantitative real-time PCR showed that MNE decreased the expression of Wnt4 and ß-catenin, while had no significant effect on PI3K, Akt, and PTEN expression. The MNE did not exhibit antiproliferative activity against HepG2 liver cancer cells. In conclusion, MNE exhibits a hepatoprotective effect through inhibiting oxidative stress and Wnt4/ß-catenin pathway and therefore prolongs the survival of rats with HCC.

Effects of Rhus coriaria L. hydroalcoholic extract on the lipid and antioxidant profile in high fat diet-induced hepatic steatosis in rats.

Oxidative stress is related to increased fat deposition in the liver, known as hepatic steatosis. The present study is an evaluation of the anti-oxidative and antihyperlipidemic effects of the hydroalcoholic extract of Rhus coriaria L. (HARE) in rats on a high-fat diet (HFD). Twenty male Wistar rats were divided into four groups: control, HFD, HFD + HARE 50 mg/kg/day, and HFD + HARE 250 mg/kg/day for 12 weeks. Animals were weighed weekly and treated with the HARE extract for 12 weeks by gavage. Subsequently, the histopathological changes, oxidative markers, and lipid profile were evaluated. Statistical analysis was performed using the one-way analysis of variance (ANOVA) for multiple comparisons. First, the active ingredients of the extract were determined by HPLC. Then, the levels in the serum lipid profile (TG, cholesterol, HDL, and LDL) in rats fed with the HFD + HARE were analyzed where a significant reduction was observed. The HFD proved to increase the activity of the liver enzymes, the serum lipid levels, and the malondialdehyde (MDA) level. The ferric-reducing antioxidant activity power (FRAP), catalase (CAT), and superoxide dismutase (SOD) catalytic activity were reduced in the liver homogenate of HFD rats compared to the controls. Additionally, the aforementioned liver enzymes activities were reduced in response to HARE. Evaluation of oxidative stress determined a reduction in the MDA level while a raised FRAP was confirmed. In accordance with the present results, histopathological observations have also demonstrated that HARE ameliorated grade-1 hepatic steatosis induced by HFD. Taken together, the findings of this study introduce HARE as a future potential therapeutic agent in treating hepatic steatosis and reducing oxidative damages of an HFD in the liver.

Acute and sub-acute toxicity evaluation of the root extract of Rheum turkestanicum Janisch.

Despite the widespread use of Rheum turkestanicum in herbal medicine, no study has yet examined its in vivo toxicity. The aim of this study is to evaluate the acute and sub-acute toxicity of hydroalcoholic extract of R. turkestanicum root. In acute toxicity experiment, female and male mice (n = 5/group/sex) were orally administrated with the extract at single doses of 300, 2000 and 3000 mg/kg and observed for 14 days. In the sub-acute study, the extract was orally administered daily at doses of 100 and 400 mg/kg to male rats (n = 8) for 4 weeks. During the acute toxicity test, there were no deaths or any signs of toxicity observed after administration of the R. turkestanicum extract at 300 mg/kg, which was the no-observed-adverse-effect level (NOAEL). The extract at a dose of 3000 mg/kg led to the death of one female and one male mouse (LD50 > 3000 mg/kg). In sub-acute toxicity experiment, the extract induced no mortality or significant changes in body weight, general behaviors, hematological parameters, serum biochemical factors (related to the kidney and liver function), and histopathology of the heart, liver, kidney, and brain up to the highest dose tested of 400 mg/kg (NOAEL). High-performance liquid chromatography-mass spectrometry revealed the presence of phenolic compounds, flavonoids, alkanes, and anthraquinones in the extract. In conclusion, short-term use of R. turkestanicum root does not appear to produce significant toxicity up to a dose of 400 mg/kg.

Administration of Nigella sativa during neonatal and juvenile growth period improved liver function of propylthiouracil-induced hypothyroid rats.

Aim: Propylthiouracil (PTU) is frequently used as an antithyroid medication. It is also commonly used to induce hypothyroidism in rodents. PTU administration and hypothyroidism have been shown to affect the liver function. Nigella sativa (NS) has been suggested to have antioxidant and hepatoprotective effects. The objective of this study was to investigate the effects of NS extract administration during neonatal and juvenile growth period on liver function of PTU-induced hypothyroid rats.Methods: The pregnant rats were kept in separate cages. After delivery, the mothers and their offspring were randomly divided into five groups and were treated with the following programs: (1) control; (2) PTU, 0.005% in their drinking water (3-5); PTU-plus 100, 200, or 400 mg/kg NS extract. After lactation period, the offspring continued to receive the same experimental treatment for the first 8 weeks of their life. Ten offspring of each group were randomly selected and weighted at days 10, 30, and 60 after delivery. Their blood samples were collected and the liver tissues were removed.Results: Malondialdehyde (MDA) concentration was increased while, thiol concentration and superoxide dismutase (SOD) and catalase (CAT) activity were decreased in the liver tissues of PTU-treated rats. Serum aspartate amino transferase (AST), alkaline phosphatase (ALK-P), and alanine aminotransferase (ALT) levels in the PTU group were higher than the control group. Treatment with 200 and 400 mg/kg decreased MDA while increasing thiol concentration in the liver tissues compared to the PTU group. Treatment with all doses of the extract decreased serum ALK-P concentration compared with the PTU group. Treatment with 400 mg/kg NS increased CAT and SOD concentrations in the liver tissues and decreased serum AST and ALT concentrations compared to the PTU group. PTU decreased body weight gain of offspring and while, the extract increased the body weight gain of offspring rats.Conclusion: The results of this study demonstrated that administration of NS hydroalcoholic extract in the neonatal and juvenile growth period has an improving effect on the liver function of PTU- induced hypothyroid rats.

Pharmacological properties of Rheum turkestanicum Janisch.

Medicinal herbs have been increasingly used worldwide for diseases prevention and treatment. Rheum turkestanicum Janisch. is a perennial shrub of the Polygonaceae family. Genus Rheum includes more than 60 species growing around the world which are used in foods and traditional medicines. R. turkestanicum is believed to be able to improve different kinds of disorders including diabetes, hypertension, jaundice and cancer. In recent years, this medicinal plant has been a subject of many experimental studies to document its health-beneficial properties. These studies have revealed antidiabetic, anticancer, nephroprotective, cardioprotective, and hepatoprotective properties of R. turkestanicum. The presence of flavonoids (e.g. epicatechin and quercetin) and anthraquinones (e.g. chrysophanol, physcion, and emodin) in R. turkestanicum justifies its health-beneficial effects. Nevertheless, possible therapeutic applications and safety of this plant still need to be elucidated in further clinical studies.

Therapeutic Potential of Curcumin in the Treatment of Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor. Despite standard multimodality treatment, the highly aggressive nature of GBM makes it one of the deadliest human malignancies. The anti-cancer effects of dietary phytochemicals like curcumin provide new insights to cancer treatment. Evaluation of curcumin's efficacy against different malignancies including glioblastoma has been a motivational research topic and widely studied during the recent decade. In this review, we discuss the recent observations on the potential therapeutic effects of curcumin against glioblastoma. Curcumin can target multiple signaling pathways involved in developing aggressive and drug-resistant features of glioblastoma, including pathways associated with glioma stem cell activity. Notably, combination therapy with curcumin and chemotherapeutics like temozolomide, the GBM standard therapy, as well as radiotherapy has shown synergistic response, highlighting curcumin's chemo- and radio-sensitizing effect. There are also multiple reports for curcumin nanoformulations and targeted forms showing enhanced therapeutic efficacy and passage through blood-brain barrier, as compared with natural curcumin. Furthermore, in vivo studies have revealed significant anti-tumor effects, decreased tumor size and increased survival with no notable evidence of systemic toxicity in treated animals. Finally, a pharmacokinetic study in patients with GBM has shown a detectable intratumoral concentration, thereby suggesting a potential for curcumin to exert its therapeutic effects in the brain. Despite all the evidence in support of curcumin's potential therapeutic efficacy in GBM, clinical reports are still scarce. More studies are needed to determine the effects of combination therapies with curcumin and importantly to investigate the potential for alleviating chemotherapy- and radiotherapy-induced adverse effects.

A Randomized Controlled Trial of a Herbal Compound for Improving Metabolic Parameters in Diabetic Patients with Uncontrolled Dyslipidemia.

OBJECTIVE: The aim of this randomized controlled trial was to investigate the effects of a polyherbal compound consisting of Aloe vera, black seed, fenugreek, garlic, milk thistle, and psyllium on diabetic patients with uncontrolled dyslipidemia. METHODS: Fifty patients with type 2 diabetes who had dyslipidemia in spite of statin therapy were randomly allocated to two groups: control group (n = 25) receiving a conventional therapy with hypolipidemic and hypoglycemic drugs and intervention group (n = 25) receiving both the conventional therapy and the herbal compound (one sachet twice daily) for 12 weeks. Each sachet contained 300 mg of Aloe vera leaf gel, 1.8 g of black seed, 300 mg of garlic, 2.5 g of fenugreek seed, 1 g of psyllium seed, and 500 mg of milk thistle seed. RESULTS: The levels of serum triglyceride, total cholesterol, low-density lipoprotein, and HbA1c showed a significant in-group improvement in the intervention group. However, the effects of the herbal compound on fasting blood glucose remained insignificant. The compound had no unwanted effect on the kidney function parameters (urea, creatinine) and serum liver enzymes (alanine aminotransferase and aspartate transaminase). CONCLUSION: The tested herbal compound, as an add-on to statin therapy, was effective in lowering the serum lipids in diabetic patients with uncontrolled dyslipidemia.

Effect of Capparis spinosa Extract on Metabolic Parameters in Patients with Type-2 Diabetes: A Randomized Controlled Trial.

BACKGROUND: Experimental studies have reported beneficial effects of Capparis spinosa L., a perennial shrub from the Capparidaceae family, on the glycemic status and serum lipids in diabetic animals. OBJECTIVE: The aim of the present randomized triple-blind placebo-controlled clinical trial was to investigate the safety and efficacy of C. spinosa oxymel on blood glucose, lipid profile, and other diagnostic indexes of metabolic syndrome in patients with poorly controlled type 2 diabetes. METHOD: The C. spinosa oxymel was prepared by adding hydroalcoholic extract of C. spinosa fruit to simple oxymel (a mixture of grape vinegar and lactulose). Thirty diabetic patients with metabolic syndrome whose glycemic status was not controlled despite receiving full doses of oral hypoglycemic agents did not want to start insulin therapy and were randomly allocated to three groups to receive placebo, simple oxymel, or C. spinosa oxymel (10 mL/thrice daily for 3 months). All patients continued conventional therapy with hypolipidemic, antihyperlipidemic, and antihypertensive drugs during the study. RESULTS: C. spinosa oxymel significantly decreased the body weight and body mass index at the end of the study compared to the baseline. While the patients in the placebo and simple oxymel groups displayed further increase in the level of FBG or PPBG, administration of C. spinosa oxymel inhibited the progression of hyperglycemia. Nevertheless, there was not a significant difference between placebo and intervention groups regarding HbA1c at the end of the study. C. spinosa oxymel had no significant effect on the serum cholesterol but inhibited the progression of hypertriglyceridemia during the study. There were no significant changes in creatinine, microalbuminuria, AST, ALT, and ALP values following C. spinosa treatment, suggesting that it had no unwanted effects on kidney and liver function. CONCLUSION: The results suggest that although C. spinosa oxymel cannot enhance the effects of hypoglycemic and hypolipidemic drugs, it can prevent further increase of blood glucose and triglycerides in patients with poorly controlled diabetes.

Study of the mechanisms of crocetin-induced differentiation and apoptosis in human acute promyelocytic leukemia cells.

Crocetin, the major carotenoid in saffron, exhibits potent anticancer effects. However, the antileukemic effects of crocetin are still unclear, especially in primary acute promyelocytic leukemia (APL) cells. In the current study, the potential antipromyelocytic leukemia activity of crocetin and the underlying molecular mechanisms were investigated. Crocetin (100 µM), like standard anti-APL drugs, all-trans retinoic acid (ATRA, 10 µM) and As2 O 3 (arsenic trioxide, 50 µM), significantly inhibited proliferation and induced apoptosis in primary APL cells, as well as NB4 and HL60 cells. The effect was associated with the decreased expressions of prosurvival genes Akt and BCL2, the multidrug resistance (MDR) proteins, ABCB1 and ABCC1 and the inhibition of tyrosyl-DNA phosphodiesterase 1 (TDP1), while the expressions of proapoptotic genes CASP3, CASP9, and BAX/BCL2 ratio were significantly increased. In contrast, crocetin at relatively low concentration (10 µM), like ATRA (1 µM) and As 2 O 3 (0.5 µM), induced differentiation of leukemic cells toward granulocytic pattern, and increased the number of differentiated cells expressing CD11b and CD14, while the number of the immature cells expressing CD34 or CD33 was decreased. Furthermore, crocetin suppressed the expression of clinical marker promyelocytic leukemia/retinoic acid receptor-α ( PML/RARα) in NB4 and primary APL cells, and reduced the expression of histone deacetylase 1 ( HDAC1) in all leukemic cells. The results suggested that crocetin can be considered as a candidate for future preclinical and clinical trials of complementary APL treatment.

Effects of standardized extracts of Lamium album and Urtica dioica on rat tracheal smooth muscle contraction.

OBJECTIVE: Diseases of the respiratory system are one of the main causes of death and include situation such as chronic obstructive pulmonary disease, pneumonia or asthma. Medicinal plants have beneficial effects on multiple diseases include respiratory disorders like asthma and bronchitis. The aim of this study was to evaluate the effects of U. dioica and L. Album on tracheal smooth muscle contraction. MATERIAL AND METHODS: Hydroalcoholic extracts of L. Album and U. Dioica aerial parts were prepared by maceration method and standardized based on their total phenol content. The effect of the extracts on the KCl-induced contraction of rat trachea was examined in an organ bath chamber. Data was analyzed with spss software 22. RESULTS: The extract of L. Album (5 mg/ml), similar to theophylline (20 mM), significantly reduced the KCl-induced tracheal contraction. On the other hand, U. Dioica (1 mg/ml and 5 mg/ml) augmented the KCl-induced contraction. CONCLUSION: The relaxant effect of L. Album on the trachea makes it as a candidate for the managing patients with asthma and obstructive pulmonary diseases. But because of U. Dioica potential constrictive effect on the trachea it is suggested that patients avoid consuming it.

In vivo and In vitro effects of ethanolic extract of Trigonella foenum-graecum L. seeds on proliferation, angiogenesis and tube formation of endothelial cells.

The role of angiogenesis in tumor progression and metastasis formation has been well recognized. Recent studies have reported that Trigonella foenum-graecum L. (fenugreek) seed extracts have potential anticancer properties. The current study was planned to investigate the anti-angiogenic activity of hydroalcoholic extract of fenugreek (HAEF) in vitro and in vivo. Effect of HAEF (50-3000 µg/mL) and thalidomide (200-3000 µmol/L), as a positive control, on the viability of human umbilical vein endothelial cells (HUVECs) and 3T3 fibroblast cells was assessed by thiazolyl blue tetrazolium bromide (MTT) assay. Effect of HAEF on vessel-like tube formation by HUVECs was examined in the matrigel-based assay. Furthermore, the chick chorioallantoic membrane (CAM) was used as in vivo model to study the anti-angiogenic effect of HAEF. HAEF, similar to thalidomide, significantly inhibited the viability of HUVECs and 3T3 cells dose-dependently after 24 h. Moreover, both HAEF and thalidomide significantly reduced tube formation by HUVECs in cell culture condition. In CAM model, HAEF and thalidomide caused a significant decline in the number of neovascular points and in the amount of grades 1 and 2 vessels. These findings revealed that fenugreek has cytotoxic and anti-angiogenic effects in vitro and in vivo. Therefore, this medicinal plant can be subjected to further investigations as antitumor agents.

Effects of a food product (based on Daucus carota) and education based on traditional Persian medicine on female sexual dysfunction: a randomized clinical trial.

BACKGROUND: Globally, female sexual dysfunction is a serious concern based on negative family and social consequences, high side effects of medications and lack of effective treatment. Thus, the evaluation of treatment approach for this problem is an important priority for healthcare systems. Sexual life and its related disorders are considered the main aspects of a healthy lifestyle in traditional Persian medicine (TPM). OBJECTIVE: The present study aimed to determine and compare the effects of food products containing Daucus carota, TPM-based training program, and a combination of these two interventions on the improvement of female sexual dysfunction. METHODS: This randomized clinical trial was conducted on 96 women with sexual dysfunction based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-5®), aged 18-35 years who referred to the Gynecology Clinic of Mashhad University of Medical Sciences, Mashhad, Iran, during 2016 and 2017. The patients were randomly divided into three groups (n=32) and received the intervention over an eight-week period. The first group was provided with TPM-based sexual health training, the second group received 30 g of a traditional food product (wild carrot halva: mixed Daucus carota and several herbs with honey) on a daily basis, and the third group received a combination of this traditional food product plus education. Data analysis was performed using Chi square test, repeated measures ANOVA, two-way ANOVA, ANCOVA, post hoc Bonferroni, Friedman and Wilcoxon signed-rank test in SPSS version 11.5. RESULTS: According to the results of this study, there was a significant difference in terms of sexual desire (p=0.002), lubrication (p=0.002), orgasm (p=0.004) and pain (p<0.001) after eight weeks of the intervention among the three groups. CONCLUSION: The use of two interventions of TPM including a food product containing Daucus carota and this product with TPM-based education improved desire, arousal, lubrication, orgasm, satisfaction and pain in females with sexual dysfunction. Furthermore, TPM-based education alone, led to the improvement of all domains of sexual dysfunction, except for pain in the females with sexual dysfunction. TRIAL REGISTRATION: The trial was registered at the Iranian Registry of Clinical Trials with the IRCT ID: IRCT2015122425681N1). FUNDING: The present study was supported by a grant from the Research Council, Mashhad University of Medical Sciences, Mashhad, Iran (ref. no.: 941503).

The effect of a vaginal suppository formulation of dill (Anethum graveolens) in comparison to clotrimazole vaginal tablet on the treatment of vulvovaginal candidiasis.

The goal of this study was to compare the effect of Anethum graveolens (dill) vaginal suppositories and 100 mg clotrimazole vaginal tablets on vulvovaginal Candidiasis. This study was a single centre, single-blind, randomised, placebo-controlled trial, in which 60 women with microbiology-confirmed vulvovaginal candidiasis were randomly assigned to dill and clotrimazole groups. At the end of the study, the estimated prevalence of leucorrhoea, burning, and itching was 23%, 23% and 20% in dill users, respectively. This figure was 20%, 10% and 16.7% for the clotrimazole group, respectively. The difference between the two groups was not significant. 13% of suppository patients, compared with 10% of clotrimazole-treatment patients, had a positive culture, which was not significant (p = .68). According to findings, 2% dill vaginal suppositories were as effective as clotrimazole vaginal tablets in reducing both clinical and microbiological symptoms of Candidiasis. Studies with larger sample sizes are required to confirm current findings. Impact statement What is already known on the subject? Based on results from in vivo and in vitro animal studies, dill (Anethum graveolens) has anti-candida activity. What do the results of this study add? It appears that 2% dill vaginal suppositories were as effective as 100 mg clotrimazole vaginal tablets in reducing both the clinical and microbiological symptoms. What are the implications of these findings for clinical practice and further research? Obstetricians and gynaecologists can offer dill as a useful alternative to chemical drugs, especially in women who are often interested in herbal medicine, or in women who are resistant or are not allowed to use antifungal drugs.

Toxicity assessment of Ferula gummosa administration during pregnancy, lactation, and juvenile period in rat.

Ferula gummosa is widely used in traditional medicine to treat a variety of ailments. This work evaluated the safety of F. gummosa root in pregnancy, lactation, and juvenile periods. This study was performed in three parts: (1) pregnant rats were received diet containing 0 (control), 150 , or 700 mg/kg of F. gummosa root during pregnancy; (2) Lactating rats were treated with diet containing the root (0, 150, or 700 mg/kg) during lactation period; (3) juvenile rats were received 4 weeks diet containing the root (0, 150, or 700 mg/kg). F. gummosa at both doses had no significant effects on the duration of pregnancy, maternal weight, and the number of delivered pups, but at dose of 700 mg/kg decreased birthweight of the pups. In lactation period, F. gummosa had no significant effects on mortality, body weight, body length, the weight of organs, and blood biochemical parameters of offspring. In juvenile rats, food consumption, body weight, and WBCs number were decreased in treated groups. No histopathological lesions were detected in the brain, heart, liver, lungs and kidney of offspring, and juvenile rats in treated groups. LC/MS/MS analysis confirmed systemic absorption of active constituents of the root by the oral route of administration. In conclusion, F. gummosa root did not produce significant toxic effects during pregnancy, lactation, and juvenile period. But, decrease in birthweight of delivered pups and in weight gain of juvenile rats should be considered in the long-term consumption of this plant.