Effect of adlay seed extract on inflammation and fibrogenesis in human corneal activated keratocytes at transcriptional level.

Corneal activated keratocytes (CAKs) -representing the injured phenotype of corneal stromal cells- are associated with several corneal diseases. Inflammatory cytokines are the key drivers of CAK formation subsequently leading to fibrogenesis. This study aimed to investigate the effect of adlay seed extract on the expression of genes involved in inflammation (IL-6, IL-1b, LIF) and fibrogenesis (TGF-ß) in CAK cells. CAKs (106 cells/10 cm2) were exposed to methanolic (MeOH) and residual (Res) extract of adlay seed (1 mg/ml, 24 h). The control group received the vehicle solution without extract at the same time and condition. Then, RNA extraction, cDNA synthesis, and real-time PCR were performed to quantify the relative expression of IL-6, IL-1b, LIF, and TGF-ß in the treated vs. control cells. This study showed that the MeOH extract of adlay seed could significantly downregulate the expression of IL-6 and IL-1b in the CAKs, while the Res extract led to a significant decrease in TGF-ß gene expression. We showed that CAK treatment with adlay seed extract could decrease the expression of genes related to inflammation and fibrogenesis. However, the genes to be targeted depended on the method of extraction. This proof-of-concept study could provide groundwork for the treatment of corneal stromal diseases and ocular regenerative medicine in the future.

The effect of berberine and fenugreek seed co-supplementation on inflammatory factor, lipid and glycemic profile in patients with type 2 diabetes mellitus: a double-blind controlled randomized clinical trial.

BACKGROUND: Type 2 Diabetes mellitus is one of the most common chronic diseases in the world and has many complications. Due to the importance of using alternative therapies in managing symptoms of this disease, the present study was designed and conducted to investigate the effect of co-supplementation of berberine and fenugreek in patients with type 2 diabetes mellitus. METHODS: A randomized controlled clinical trial was conducted on 50 patients with type 2 diabetes mellitus. Participants were randomized in the intervention group, which received 3 capsules/day of 500 mg (300 mg of berberine + 200 mg of fenugreek seed powder) or placebo for 12 weeks. Biochemical and anthropometric variables were measured at the beginning and end of the study. RESULTS: We observed that fasting insulin, HbA1C, and hs-CRP significantly decreased in the intervention group compared to the baseline. The mean difference in insulin resistance (-0.32 vs. 0.15), fasting blood sugar (-14.40 vs. 1.68), and fasting insulin (- 2.18 vs. 1.34) were clinically significant in comparison to the control group. Almost all domains of SF-12 scores were significantly higher in the intervention group than in the placebo group. CONCLUSIONS: The combination of berberine and fenugreek seed can improve cardio-metabolic status in patients with diabetes and support the anti-diabetic and anti-inflammatory role of herb in the improvement of quality of life.

The comparison of therapeutic effect of Clobetasol propionate lotion and squill extract in alopecia areata: a randomized, double-blind clinical trial.

Alopecia areata is a chronic inflammatory disease that characterized by round or oval patches of non-scarring hair loss. From the past, Urginea maritima (white squill) was used for the treatment of hair loss in Iranian traditional medicine. We aimed the comparison of Clobetasol lotion and squill extract efficacy in treatment of alopecia areata in a randomized, double-blind clinical trial. The 42 patients were randomized into two groups. Both groups received topical squill and clobetasol lotion twice daily lotion for 12 weeks. Clinical evaluation included size of patches (using 1×1 cm2 schablone), total number of grown hair and number of terminal hair was performed every 2 weeks. Re-growth of terminal coarse hairs was evaluated using a semi-quantitative regrowth score (RGS) (0: no regrowth, 1: growth of <25%, 2: growth of 25-50%, 3: growth of 51-75%, 4: growth of >75%). There were significant differences between RGS4 in two groups after 2- and 3-month treatment (P<0.05). At the end of follow-up period, the mean hair growth rates increased significantly from 6.5 to 11.3 in squill group (P = 0.031) and it improved significantly from 10.3 to 17.9 in clobetasol group (P = 0.001). There were no significant differences between mean hair growth rates in two groups after 3-month treatment (P = 0.969). The lotion 2% of U. maritima bulbs extract showed good effect in 45% patients with patchy alopecia areata and showed moderate effect on re-growth of terminal hairs.

The Anti-melanogenesis Activities of Some Selected Red Macroalgae from Northern Coasts of the Persian Gulf.

Tyrosinase is a key enzyme in melanin production. Therefore, tyrosinase inhibitors are used in cosmetic and medicinal industries to prevent or treat overproduction of melanin such as melasma, solar lentigo and post inflammatory melanoderma. Due to safety of natural whitening agents, in the present study, in-vitro anti-tyrosinase and in-vivo anti-melanogenesis activities of some selected red macroalgae of the Persian Gulf were investigated. The effects of various concentrations (100, 250 and 500 µg/mL) of methanolic extracts of three red macroalgae including Digenea simplex (D. simplex), Laurencia papillosa, and Laurencia paniculata on the activity of diphenolase of mushroom tyrosinase were studied by using L-Dopa as substrate. Subsequently, the activity of macroalgae with high inhibitory effect on hydroxylation of L-tyrosine was investigated by mushroom tyrosinase and zebrafish model. Anti-melanogenesis effects of algae extracts were studied on zebrafish as an alternative in-vivo model. Kojic acid was used as a positive control. All the tested macroalgae showed significantly a lower inhibitory effect on activities of diphenolase and monophenolase (of mushroom tyrosinase) compared to kojic acid. D. simplex showed the most anti-tyrosinase activity in zebrafish model among the samples. D. simplex extract and Kojic acid inhibited tyrosinase activity by 43.18% and 50.45%, and decreased total melanin content of zebrafish by 47.27% and 50.21%, respectively.

An evaluation of the effects of saffron supplementation on the asthma clinical symptoms and asthma severity in patients with mild and moderate persistent allergic asthma: a double-blind, randomized placebo-controlled trial.

BACKGROUND: Asthma is a heterogeneous disease which is usually associated with chronic airway inflammation. Saffron has anti-inflammatory effects and may has beneficial effects on asthma. HYPOTHESIS: The present study was intended to survey the effects of saffron supplementation on blood pressure, lipid profiles, basophils, eosinophils and clinical symptoms in patients with allergic asthma. STUDY DESIGN: Our study was a clinical trial. METHODS: Subjects (N = 80, 32 women and 48 men, 41.25 ± 9.87 years old) with mild and moderate allergic asthma were randomized into two groups: the intervention group who received two capsules of saffron (100 mg/d), and the control group who received two capsules of placebo for 8 weeks. SPSS software (version 16.0) was used for the data analysis. RESULTS: Saffron improved the frequency of clinical symptoms of the patients (i.e., frequency of the shortness of breath during the day and night time, use of salbutamol spray, waking up due to asthma symptoms and activity limitation) in comparison to the placebo (p < 0.001). Besides, asthma severity decreased almost significantly in the saffron group (p = 0.07). It was also found that saffron, in comparison with the placebo, significantly reduced the systolic and diastolic blood pressure, triglycerides and low density lipoprotein cholesterol. Moreover, eosinophils and basophils concentration reduced in the saffron group (p = 0.06 and 0.05 respectively). CONCLUSION: Saffron seems to be an effective and safe option (in 8 weeks supplementation) to improve clinical symptoms of patients with allergic asthma but the toxicity and/or long-term effects of saffron intake are not known. Registration ID in IRCT (IRCT2017012132081N2).

The effect of evening primrose oil on fatigue and quality of life in patients with multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a chronic progressive and inflammatory disease of the central nervous system that is characterized by demyelination in the central nervous system. In regard to the prevalence of diseases and enormous costs imposed on society and the health system, finding a way to stop the progression of the disease using drugs with fewer side effects seems a serious sanitation issue to the health of the international community. This study aimed to evaluate the effect of evening primrose oil (EPO) on fatigue and quality of life in patients with MS. MATERIALS AND METHODS: In this double-blind randomized clinical trial, 52 patients with MS were chosen and categorized into 2 groups which received 2 doses of EPO and placebo. In addition, the quality of life and fatigue scale in these patients were investigated before the treatment and again 3 months after therapy. The findings were then compared between the 2 groups. RESULT: EPO consumption significantly increased cognitive function, vitality, and overall life satisfaction and also reduced pain and fatigue compared to placebo (P<0.05). CONCLUSION: Our findings indicated that EPO consumption had no impact on the quality of life in general; however, it had a significant effect on several important aspects of life quality such as the increase of cognitive function, vitality, and overall life satisfaction. It also reduced the pain and fatigue in comparison to the placebo consumption. Herbal medicines are brittle and have fewer side effects than chemical drugs. With use of this plant, reduced fatigue and improved quality of life were observed in MS patients. But the drug did not prevent the progression of the disease.

Effect of fennel vaginal cream on sexual function in postmenopausal women: A double blind randomized controlled trial.

Objective: The aim of this study was to assess the effect of fennel on sexual function in postmenopausal women. It was a randomized controlled trial in 60 postmenopausal women with sexual dysfunction who were randomly assigned to two groups receiving either fennel vaginal cream (n=30) or placebo (n=30). Vaginal atrophy in the women was assessed using symptoms such as pallor, dryness, dyspareunia, itching and burning. The pH of the vagina and cytology of the vaginal mucosa were also measured at baseline and 8 weeks after the intervention. All participants were requested to fill out the Female Sexual Function Index (FSFI) at baseline and after 8 weeks. The intervention group was requested to use fennel vaginal cream (5 grams) every night, while the control group used placebo each night for 8 weeks. The data were analyzed using the independent t-test and Chi-square, Mann-Whitney and Wilcoxon tests. All areas of sexual function including arousal, lubrication, orgasm, sexual satisfaction and pain improved in both fennel and placebo groups after 8 weeks; however, the differences in the fennel group were more evident (p<0.05). The total FSFI score was significantly higher in the fennel group compared to the control group (8.2 ±9.4 and 8.03±10.36 before the intervention and changing to 33.79±0.7 and 18.99±1.09 after the intervention in the fennel and placebo groups, respectively; p<0.001). Discussion: According to our results, fennel vaginal cream is an effective means of improving sexual activity in postmenopausal women. The use of this product in women who have sexual dysfunction and contraindications for hormone therapy is recommended.

A Review of Possible Herbal Treatment in Multiple Sclerosis in Traditional Persian Medicine.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory disease of central nervous system (CNS) and is the most common cause of neurologic disability in young adults (20-40 years old). About 2.5 million patients all over the world are suffering from MS. Common symptoms of the disease include sensory disorders, optic neuritis, and limb weakness. Following disease progression, other symptoms like fatigue, bladder disorders, and cognitive impairment also occur. Traditional Persian medicine (TPM) is an ancient medical system from 6000 years ago in Persia, where Iran was its most important state. TPM is a known humoral medical system. METHODS: In this review article, the traditional approach to MS and treatment methods in TPM literature are presented. TPM literature was written in the Persian and Arabic languages, the common scientific language of that era. Keywords defining MS were extracted from the well-known TPM books, such as Canon, Tebb-e-akbari, and Exire azam. The search covered known books from the 5th century to the 19th century. At the beginning, keywords such as Khaddar, Esterkha and Falej were considered. The search for herbal remedies was carried out according to the defined keywords in the main TPM manuscripts and especially in remedies (Mufradat) and treatment (Moalejat) TPM books, including Makhzan-ul-Adwiah, Al-abnieh Al-aghayegh Al-advie, Tuhfat-ul-Momineen, Gharabadin-e-Kabir, Gharabadine Shafaee, Tib-e-Akbari, and Exir-e-Azam. RESULTS: As the result of this review study, we managed to introduce categorized lists of herbal remedies and combinations used orally and in topical forms. Finally, comparative tables, including scientific names of plants, active components, and mechanisms showed the results of recent studies and phytotherapy research on TPM ancient remedies. CONCLUSION: Although we did not find MS in our search; however, there are some ailments with similar signs and symptoms in TPM literature. A list of various herbal medicaments has been introduced for these ailments, which should be evaluated critically during precise experimental and clinical studies.

Efficacy of Dragon's blood cream on wound healing: A randomized, double-blind, placebo-controlled clinical trial.

The blood-red sap of Dragon's blood has been used in folk medicine for fractures, wounds, inflammation, gastrointestinal disorders, rheumatism, blood circulation dysfunctions, and cancer. Existing in vitro and in vivo bioactivity of this herb on different mechanisms of healing shows strong potential of this sap in wound healing. This clinical trial study was designated to evaluate the wound healing effect of Dragon's blood on human wounds. Sixty patients, between the ages of 14-65 years, who were referred to remove their skin tag, were assigned to this double-blind, placebo-controlled, randomized clinical trial and received either Dragon's blood or a placebo cream. They were visited on the 3rd, 5th, 7th, 10th, 14th, and 20th day of the trial to check the process of healing and to measure the wound's surface. At the end of trial, there was a significant difference in the mean duration of wound healing between the two groups (p = 0.0001). The phenolic compounds and the alkaloid taspine, which exist in Dragon's-blood resin, are probably the main reasons for the wound healing property of this plant. Being natural accessible, safe, and affordable makes Dragon's blood cream, a good choice for addition to the wound healing armamentarium. Further studies on wounds with different causes and among larger populations are suggested to ensure the effectiveness and safety of Dragon's blood.

Effect of Foeniculum vulgare (fennel) vaginal cream on vaginal atrophy in postmenopausal women: A double-blind randomized placebo-controlled trial.

OBJECTIVE: Vaginal atrophy is one of the main concerns of postmenopausal women. The aim of the present study was to investigate the effect of fennel vaginal cream on vaginal atrophy in postmenopausal women in Ahvaz, Iran. MATERIALS AND METHODS: This double-blind randomized controlled trial was conducted on 60 postmenopausal women (45-65 years of age) in Ahvaz, Iran. The study participants were randomly divided into one of two groups, receiving either a placebo (n=30) or fennel 5% vaginal cream (n=30) administered as one application per day (5g/day) for 8 weeks. MAIN OUTCOME: The vaginal pH and maturation vaginal index (MVI) were measured at baseline and 8 weeks after the intervention, while the vaginal atrophy symptoms was measured at baseline and at 2, 4, and 8 weeks after the intervention. The data were analyzed using the independent t-test, chi-square test, paired sample t-test, and the generalized estimating equation. RESULTS: The number of superficial cells increased significantly in the fennel group after 8 weeks compared to the control group (76.1±15.3 vs. 11.8±8, p<0.001). The number of intermediate and parabasal cells decreased significantly in the fennel group compared to the control group (p<0.001). The vaginal pH decreased significantly at the 8-week follow-up in the fennel group compared to the control group (100% vs. 7.4%, p<0.001). All women in the fennel group had an MVI of 65-100 at the 8-week follow-up, whereas almost half (40.7%) of the women in the control group had an MVI of 50-64 (p<0.001). CONCLUSION: According to results of this study, fennel is an effective means to manage the symptoms of vaginal atrophy in postmenopausal women and is devoid of side effects. Larger studies are necessary to confirm the positive impact of fennel for vaginal conditions occurring among postmenopausal women.

Inhibitory Effects of Physalis alkekengi L., Alcea rosea L., Bunium persicum B. Fedtsch. and Marrubium vulgare L. on Mushroom Tyrosinase.

BACKGROUND: The key enzyme in the process of melanin biosynthesis is tyrosinase. Skin hyperpigmentation and browning of foods are undesirable phenomena which tyrosinase represents. Therefore, tyrosinase inhibitors have been used increasingly for medicinal and cosmetic products. OBJECTIVES: In this study, inhibitory effects of four plants including: physalis alkekengi L., Alcea rosea L., Bunium persicum B. Fedtsch. and Marrubium vulgare L. on diphenolase activity of mushroom tyrosinase were evaluated. MATERIALS AND METHODS: The inhibitory activities of hydroalcoholic extracts of plants against oxidation of L-Dopa (as a substrate) by mushroom tyrosinase were investigated. RESULTS: The hydroalcoholic extract of P. alkekengi showed the most tyrosinase inhibitory effect with IC50 of 0.09 mg/mL vs. 0.38, 0.38 and 2.82 mg/mL of B. persicum, A. rosea and M. vulgare, respectively. M. vulgare exhibited uncompetitive inhibition and other plants showed mixed type inhibition on mushroom tyrosinase. CONCLUSIONS: All plants could inhibit mushroom tyrosinase, but more investigations on human tyrosinase and clinical studies are needed.

Evaluation of drying process on the composition of black pepper ethanolic extract by high performance liquid chromatography with diode array detector.

BACKGROUND: Black pepper (Piper nigrum) is one of the well-known spices extensively used worldwide especially in India, and Southeast Asia. The presence of alkaloids in the pepper, namely, piperine and its three stereoisomers, isopiperine, chavicine and isochavicine are well noticed. OBJECTIVES: The current study evaluated the effect of lyophilization and oven drying on the stability and decomposition of constituents of black pepper ethanolic extract. MATERIALS AND METHODS: In the current study ethanolic extract of black pepper obtained by maceration method was dried using two methods. The effect of freeze and oven drying on the chemical composition of the extract especially piperine and its three isomers were evaluated by HPLC analysis of the ethanolic extract before and after drying processes using diode array detector. The UV Vis spectra of the peaks at piperine retention time before and after each drying methods indicated maximum absorbance at 341.2 nm corresponding to standard piperine. RESULTS: The results indicated a decrease in intensity of the chromatogram peaks at approximately all retention times after freeze drying, indicating a few percent loss of piperine and its isomers upon lyophilization. Two impurity peaks were completely removed from the extract. CONCLUSIONS: In oven dried samples two of the piperine stereoisomers were completely removed from the extract and the intensity of piperine peak was increased.

The Antioxidant Capacity and Anti-diabetic Effect of Boswellia serrata Triana and Planch Aqueous Extract in Fertile Female Diabetic Rats and the Possible Effects on Reproduction and Histological Changes in the Liver and Kidneys.

BACKGROUND: Boswellia serrata has been used in a wide variety of diseases, including diabetes mellitus and inflammatory diseases. OBJECTIVES: This study focused on the effects of Boswellia serrata aqueous extract on blood glucose and the complications of diabetes in the liver and kidneys and examined the impact of plant on reproduction in diabetic rats. MATERIALS AND METHODS: The antioxidant capacity of plant extract was performed using FRAP assay. Diabetic and control rats were administered 200, 400, and 600 mg/kg Boswellia serrata extract. Vaginal plaque was mentioned as a positive sign of pregnancy ;and treatment started with extract or vehicle from 1th to 17th day of gestation by gastric gavage. Blood glucose was measured during 17 days. RESULTS: The Administration of Boswellia serrata in diabetic rats significantly decreased the level of blood glucose and HbA1c after 17th days (P ≤ 0.01). In diabetic group that received no treatment, the abortion of fetus spontaneous was 19.14%. The percentage of absorptions significantly was elevated in vehicle-treated diabetic rats, in comparison with vehicle- treated healthy rats. In the diabetic group, separated necrosis of hepatocytes, anarchism of liver plates, and lymphocytic inflammation were improved. Diabetic complications were not seen and the severity of damage was reduced. These damages include: lymphocytic inflammation in the port areas, irregularities, apoptosis of liver cells, and dilatation of the sinusoids. CONCLUSIONS: The results suggest that Boswellia serrata extract has the antidiabetic effects and can prevent the complications of diabetes in the kidneys and liver.

Putrescine N-methyltransferases--a structure-function analysis.

Putrescine N-methyltransferase (PMT) is a key enzyme of plant secondary metabolism at the start of the specific biosynthesis of nicotine, of tropane alkaloids, and of calystegines that are glycosidase inhibitors with nortropane structure. PMT is assumed to have developed from spermidine synthases (SPDS) participating in ubiquitous polyamine metabolism. In this study decisive differences between both enzyme families are elucidated. PMT sequences were known from four Solanaceae genera only, therefore additional eight PMT cDNA sequences were cloned from five Solanaceae and a Convolvulaceae. The encoded polypeptides displayed between 76% and 97% identity and typical amino acids different from plant spermidine synthase protein sequences. Heterologous expression of all enzymes proved catalytic activity exclusively as PMT and K (cat) values between 0.16 s(-1) and 0.39 s(-1). The active site of PMT was initially inferred from a protein structure of spermidine synthase obtained by protein crystallisation. Those amino acids of the active site that were continuously different between PMTs and SPDS were mutated in one of the PMT sequences with the idea of changing PMT activity into spermidine synthase. Mutagenesis of active site residues unexpectedly resulted in a complete loss of catalytic activity. A protein model of PMT was based on the crystal structure of SPDS and suggests that overall protein folds are comparable. The respective cosubstrates S-adenosylmethionine and decarboxylated S-adenosylmethionine, however, appear to bind differentially to the active sites of both enzymes, and the substrate putrescine adopts a different position.