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This systematic review evaluated a total of 31 included human intervention studies that have assessed methods to improve quercetin bioavailability from different formulations and food matrices using urine or blood samples up to July 2024. The bioavailability of quercetin in humans was affected by several factors. 1) Chemical structure: Quercetin-3-O-oligoglucosides exhibited 2-fold higher bioavailability than quercetin-3-O-glucoside, 10-fold higher than quercetin-3-O-rutinoside and ∼ 20-fold higher than quercetin aglycone. 2) Modification of physicochemical properties: In comparison to quercetin aglycone, the quercetin-3-O-glucoside-γ-cyclodextrin inclusion complex showed a 10.8-fold increase in bioavailability, while the self-emulsifying fenugreek galactomannans and lecithin encapsulation, and lecithin phytosome, showed a 62- and 20.1-fold increase, respectively. 3) Food matrix effects: the addition of dietary fats and fibre increased bioavailability by ∼2-fold. This review summarises key factors that enhance quercetin bioavailability, contributing to the development of more effective and practical quercetin supplements or functional foods for better bioactivity of quercetin in humans.

Saffron and fenugreek have been shown to have an effect on lowering blood glucose; therefore, this study aims to evaluate the effects of using saffron and fenugreek on blood glucose control. PubMed, Cochrane Library, Scopus, and Web of Science databases were searched for relevant articles. Articles on the use of saffron or fenugreek to control blood glucose were selected in compliance with PRISMA guidelines. R software was used for statistical analysis. The mean difference (MD) and the standardized MD (SMD) were adopted, and subgroup analyses were performed according to patient's clinical condition. Nineteen studies comprised this meta-analysis. Overall, using fenugreek decreased fasting blood glucose (FBG) (SMD: -0.90; 95%CI: -1.43 to -0.38; I2 = 87%; p < 0.001), postprandial blood glucose (PPBG) (SMD: -1.13; 95%CI: -1.99 to -0.28; I2 = 94%; p < 0.001), and glycated hemoglobin (HbA1c) (SMD: -0.43; 95%CI: -0.75 to -0.12; I2 = 20%; p = 0.29). Saffron supplementation reduced FBG (MD: -9.06 mg/dl; 95%CI: -16.25 to -1.86; I2 = 40%; p = 0.12) and HbA1c (MD: -0.19%; 95%CI: -0.23 to -0.14; I2 = 0%; p > 0.99). Our results show that using saffron and fenugreek can reduce FBG, PPBG, and HbA1c; however, there are some shortcomings that require attention for these results. Further high-quality studies should be conducted to establish the clinical efficacy of herbal medicines. © 2023 John Wiley & Sons Ltd.

INTRODUCTION: Cardiovascular diseases (CVDs) are growing health issues worldwide. Hypertension (HTN) is one of the most common among CVDs in all populations. Fenugreek has recently been the center of multiple investigations. AIM: In this systematic review and meta-analysis, we aimed at gathering and summing up the existing literature regarding the impact of fenugreek seed on systolic blood pressure (SBP) and diastolic blood pressure (DBP). METHODS: All major databases (MEDLINE, Cochrane library, EMBASE, and Web of Science) were searched from inception up to 28 June 2022. Relevant randomized controlled trials (RCTs) meeting the inclusion criteria were included and the required data was extracted. The pooled effects were reported as weighted mean differences (WMDs). I-squared test was used to detect between-study heterogeneities. Subgroup analyses were conducted to find sources of heterogeneities. P-values < 0.05 were considered as statistically significant. RESULTS: Six RCTs including a total of 373 participants were included in the final meta-analysis. Fenugreek seed supplementation significantly reduced SBP (WMD: 3.46 mmHg, 95% CI - 6.33, - 0.59, P=0.018), but not DBP (WMD: 3.19 mmHg; 95% CI, - 5.82 to 12.21, P=0.488). Subgroup analyses showed that fenugreek seed administered in dosages ≥ 15 g/day and durations ≤ 12 weeks significantly reduced SBP and DBP. CONCLUSION: Supplementation with fenugreek seed, especially in dosages ≥ 15 g/day and durations ≤ 12 weeks, might play a role in reducing SBP, but not DBP. However, further investigations are warranted to ensure the clinical relevance of these findings. © 2023. Italian Society of Hypertension.

Metabolic syndrome (MetS) is a cluster of metabolic disorders with a heavy disease burden. Fenugreek was reported to be effective in some components of MetS. Therefore, a comprehensive review and meta-analysis of randomized controlled trials was conducted to study the effects of fenugreek on MetS indices. From the beginning until August 2022, PubMed, Embase, Scopus, and Web of science were searched. Data were analyzed using the random-effect model, and presented as weighted mean difference (WMD) and associated 95 % confidence interval (CI). This meta-analysis comprised from a total of 29 eligible RCTs with 31 arms measuring fasting plasma glucose (FPG), Triglyceride (TG), high-density lipoprotein (HDL), waist circumference (WC), systolic blood pressure (SBP), and diastolic blood pressure (DBP). The results indicated significant improving effects of fenugreek on FPG (WMD: -16.75 mg/dL; 95 % CI: -23.36, -10.15; P < 0.001), TG (-20.12 mg/dL; 95 % CI: -34.238, -5.994; P < 0.001), HDL (WMD: 3.55 mg/dL; 95 % CI: 1.98, 5.12; P < 0.001), WC (WMD: -2.51; 95 % CI: -3.78, -1.24; P < 0.001) and SBP (WMD: -3.45 mmHg; 95 % CI: -6.38, -0.52; P = 0.021); However the effect on DBP (WMD: 3.17; 95 % CI: -5.40, 11.73; P = 0.469) and BMI (WMD: -0.40 kg/m2; 95 % CI: -1.114, 0.324; P = 0.281) was not significant. Administration of fenugreek can meaningfully reduce FPG, TG, WC, and SBP and increase HDL. The overall results support possible protective and therapeutic effects of fenugreek on MetS parameters.

BACKGROUND: Many women express concern about their ability to produce enough milk, and insufficient milk is frequently cited as the reason for supplementation and early termination of breastfeeding. When addressing this concern, it is important first to consider the influence of maternal and neonatal health, infant suck, proper latch, and feeding frequency on milk production, and that steps be taken to correct or compensate for any contributing issues. Oral galactagogues are substances that stimulate milk production. They may be pharmacological or non-pharmacological (natural). Natural galactagogues are usually botanical or other food agents. The choice between pharmacological or natural galactagogues is often influenced by familiarity and local customs. Evidence for the possible benefits and harms of galactagogues is important for making an informed decision on their use. OBJECTIVES: To assess the effect of oral galactagogues for increasing milk production in non-hospitalised breastfeeding mother-term infant pairs. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), Health Research and Development Network - Phillippines (HERDIN), Natural Products Alert (Napralert), the personal reference collection of author LM, and reference lists of retrieved studies (4 November 2019). SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs (including published abstracts) comparing oral galactagogues with placebo, no treatment, or another oral galactagogue in mothers breastfeeding healthy term infants. We also included cluster-randomised trials but excluded cross-over trials. DATA COLLECTION AND ANALYSIS: We used standard Cochrane Pregnancy and Childbirth methods for data collection and analysis. Two to four review authors independently selected the studies, assessed the risk of bias, extracted data for analysis and checked accuracy. Where necessary, we contacted the study authors for clarification. MAIN RESULTS: Forty-one RCTs involving 3005 mothers and 3006 infants from at least 17 countries met th

Various studies have shown that Trigonella foenum-graecum (fenugreek) supplementation has lipid-lowering activity. This meta-analysis was performed to evaluate the effect of fenugreek supplementation on human serum lipid profile. Data sources were PubMed, EMBASE, Scopus, and Coherence library which were searched systematically from January 2000 up to December 2019. Inclusion criteria were randomized clinical trial (RCT) study design, at least one of lipid profile components (triglyceride [TG], total cholesterol [TC], low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol) levels measured before fenugreek use and one of the lipid components level reported as result. The pooled weighted mean difference (MD) and its 95% confidence interval (CI) were calculated and pooled using a random-effect model. Only articles published in English were considered. Fifteen RCTs involving 281 cases consumed fenugreek and 255 control cases in controlled group (11 articles) and 136 cases in uncontrolled group (4 articles) were analyzed in our study. Pooled data of indicated a significant impact of fenugreek supplementation on lowering TC (-1.13 [-1.88, -0.37]; p = .003), low-density lipoprotein (LDL) (-1.26 [-2.09, -0.43]; p = .003), and TG (-1.07 [-1.82, -0.33]; p = 0.005) and increasing the high-density lipoprotein (HDL) level (0.70 [0.07, 1.34]; p = .03) compared with the control group. There were no significant differences in TC, TG, and LDL between pre- and post-fenugreek studies in the noncontrolled studies however, the result of combination of four studies without control group showed a significant increase in mean HDL (0.81 [0.33,1.29]; p-value = .001). The results of subgroup analysis showed that the fenugreek reduced the TG and LDL and increases HDL levels in diabetic subjects more effectively. Fenugreek supplementation significantly improved lipid profile (LDL, TG, TC, and HDL). It could be considered as an effective lipid-lowering medicinal plant. Further high-quality studies are needed to firmly establish the clinical efficacy of the plant. © 2020 John Wiley & Sons, Ltd.

ETHNOPHARMACOLOGICAL RELEVANCE: Fenugreek is a traditional herbal medicine that has been used for centuries to treat hyperglycemia, muscle spasms, gastritis, constipation, edema, and other metabolic disorders. Recently, lipid-lowering effects of fenugreek have been identified. AIM OF THE STUDY: The aim of this systematic review and meta-analysis was to determine and clarify the impact of fenugreek supplementation on anthropometric indices and serum lipid levels. MATERIALS AND METHODS: We searched PubMed, Scopus, ISI Web of Science, Cochrane Library, and Google Scholar from inception to June 2019 using relevant keywords. All randomized controlled trials (RCTs) investigating the effects of fenugreek on anthropometric indices and plasma lipids in adults were included. A random-effects model was used for quantitative data synthesis. A sensitivity analysis was conducted using the leave-one-out method. RESULTS: A meta-analysis of 12 RCTs (14 arms) with 560 participants suggested a significant decrease in plasma concentrations of total cholesterol (WMD = -9.371 mg/dL; 95% CI: -15.419, -3.323, p = 0.002), triglycerides (WMD = -13.776 mg/dL; 95% CI: -26.636, -0.916, p = 0.036), and low density lipoprotein cholesterol (WMD = -6.590 mg/Dl; 95% CI: -13.042, -0.137, p = 0.045), as well as an increase in plasma high density lipoprotein cholesterol (WMD = 3.501 mg/dL; 95% CI: 1.309, 5.692, p = 0.002), while body weight (WMD = 0.223 kg; 95% CI: -0.509, 0.955, p = 0.551) and body mass index (WMD = 0.091 kg/m2; 95% CI: -0.244, 0.426, p = 0.596) were not altered. CONCLUSION: Fenugreek supplementation improved lipid parameters in adults. However, to confirm these results, more studies, particularly among hyperlipidemic patients, are needed.

Different types of glycosides extract of fenugreek have shown androgenic and anabolic effect in male. The aim of the study was to evaluate the effect of fenugreek extract on total testosterone levels in male. Medline via PubMed, Scopus databases, Cochrane Library, Web of Science, and Google Scholar were searched up to November 2018 for randomized clinical trials comparing intake of fenugreek extract with control group. Data on change in serum total testosterone were pooled using random-effects models. A total of four trials were included. Fenugreek extract has a significant effect on total serum testosterone. Results from clinical trials suggest that fenugreek extract supplement has an effect on serum total testosterone levels in male. © 2020 John Wiley & Sons, Ltd.

BACKGROUND: Dysmenorrhoea refers to painful menstrual cramps and is a common gynaecological complaint. Conventional treatments include non-steroidal anti-inflammatory drugs (NSAIDs) and oral contraceptive pills (OCPs), which both reduce myometrial activity (contractions of the uterus). A suggested alternative approach is dietary supplements. We used the term 'dietary supplement' to include herbs or other botanical, vitamins, minerals, enzymes, and amino acids. We excluded traditional Chinese medicines. OBJECTIVES: To determine the efficacy and safety of dietary supplements for treating dysmenorrhoea. SEARCH METHODS: We searched sources including the Cochrane Gynaecology and Fertility Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, AMED, PsycINFO (all from inception to 23 March 2015), trial registries, and the reference lists of relevant articles. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of dietary supplements for moderate or severe primary or secondary dysmenorrhoea. We excluded studies of women with an intrauterine device. Eligible comparators were other dietary supplements, placebo, no treatment, or conventional analgesia. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, performed data extraction and assessed the risk of bias in the included trials. The primary outcomes were pain intensity and adverse effects. We used a fixed-effect model to calculate odds ratios (ORs) for dichotomous data, and mean differences (MDs) or standardised mean differences (SMDs) for continuous data, with 95% confidence intervals (CIs). We presented data that were unsuitable for analysis either descriptively or in additional tables. We assessed the quality of the evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methods. MAIN RESULTS: We included 27 RCTs (3101 women). Most included studies were conducted amongst cohorts of students with primary dysmenorrhoea in their late teens or early twenties. Twenty-two studies were conducted in Iran and the rest were performed in other middle-income countries. Only one study address

ETHNOPHARMACOLOGICAL RELEVANCE: A variety of herbs has been used in traditional medicine for the treatment of diabetes. However, evidence is limited regarding the efficacy of individual herbs for glycemic control. We performed a systematic review and meta-analysis to evaluate the effect of herbal supplement on glycemic control in type 2 diabetes. MATERIALS AND METHODS: Randomized controlled trials were identified through electronic searches (MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials) up until February 2011, historical searches of relevant articles and personal contact with experts in the area. Studies were included in the meta-analysis if they were (1) randomized placebo-controlled trial of single herb aimed at assessing glycemic control in type 2 diabetes, (2) of at least 8 weeks duration, and (3) reporting HbA(1c). Treatment effect was estimated with mean difference in the final value of HbA(1c) and FBG between the treatment and the placebo groups. RESULTS: Nine randomized, placebo-controlled trials (n = 487 patients) were identified. Ipomoea batatas, Silybum marianum and Trigonella foenum-graecum significantly improved glycemic control, whereas Cinnamomum cassia did not. The pooled mean differences in HbA(1c) were -0.30% (95% CI -0.04% to -0.57%; P = 0.02), -1.92% (95% CI -0.51% to -3.32%; P = 0.008), and -1.13% (95% CI -0.11% to -2.14%; P = 0.03), respectively, for Ipomoea batatas, Silybum marianum, and Trigonella foenum-graecum. The corresponding values for FBG were -10.20mg/dL (95% CI -5.32 mg/dL to -15.08 mg/dL; P<0.0001) and -38.05 mg/dL (95% CI -9.54 mg/dL to -66.57 mg/dL; P = 0.009), respectively, for Ipomoea batatas and Silybum marianum. CONCLUSIONS: The current evidence suggests that supplementation with Ipomoea batatas, Silybum marianum, and Trigonella foenum-graecum may improve glycemic control in type 2 diabetes. Such effect was not observed with Cinnamomum cassia. Given the limitations of the available studies and high heterogeneity of the study results for milk thistle and fenugreek, further high quality, large controlled trials using standardized preparation are warranted to better elucidate the effects of these herbs o

INTRODUCTION: Breast milk is the preferred source of nutrition for premature infants. Galactagogues are used in initiation, induction, and maintenance of lactation. This study examined the effectiveness of fenugreek on prolactin levels and milk volume (primary outcomes), neonatal weight gain, breastfeeding satisfaction, and side effects (secondary outcomes). METHODS: This triple-blind randomized controlled trial was conducted on 68 mothers with preterm newborns less than 32 weeks in Al-Zahra and Taleghani hospitals in Tabriz-Iran. Participants were randomly allocated into fenugreek and placebo groups. About 500 mg of fenugreek and placebo capsules were administered to the participants three times a day, from the fifth day after delivery to the 14th day. Breast milk volume was measured on the fourth day after delivery (one day before the intervention), the seventh day, and the fifteenth day after the intervention. Prolactin levels were measured in the morning before and after the intervention. RESULTS: On the seventh day of the intervention, milk volume was significantly higher in the fenugreek group than in the placebo group (p =0.017). Nevertheless, no statistically significant difference was observed between groups in milk volume (p =0.073) and prolactin level (p =0.324) on day 15. Moreover, no statistically significant difference was observed between groups regarding newborn weight after intervention (p =0.172) or satisfaction with breastfeeding (p =0.484). None of the participants reported any side effects. CONCLUSIONS: Fenugreek increases milk volume but has no significant effect on prolactin levels. Further trials with larger sample sizes should be performed to obtain conclusive results. CLINICAL TRIAL REGISTRATION NUMBER: IRCT20120718010324N62.

BACKGROUND AND OBJECTIVES: Evidence suggests that bioactive components present in plant foods have beneficial effects. Fenugreek is commonly used in Indian culinary practices and can help to keep blood sugar levels under control. The objective of this study was to assess the efficacy of defatted fenugreek seed flakes (FenuflakesTM) on the 24-hour glycaemic response (Incremental Area Under the Curve, iAUC), variability (Mean Amplitude Glycaemic Excursion assessed by Continuous Glucose Monitoring system) in participants with type 2 diabetes. METHODS AND STUDY DESIGN: Twenty-one type 2 diabetes participants, aged 42 to 50 years, were provided with 5-day cyclic iso-caloric diets for 14 days without (control diet) and with 30 g of FenuflakesTM (test diet) in a randomized crossover trial. The Abbott Pro sensor recorded interstitial glucose concentration every 15 minutes consecutively for 14 days in the participants. Additionally, fasting plasma glucose and glycated hemoglobin (HbA1c) were assessed at the baseline and end of the study. RESULTS: 15 out of 21 participants completed the randomized control and test diet feeding periods as per protocol. There was a significant reduction in 24-hour iAUC (p=0.02) and mean amplitude glycemic excursions (p=0.006) in the test diet as compared to control diet. Furthermore, within the test diet, there was a significant reduction in fasting plasma glucose and HbA1c (p<0.05) at the end of the 14-day intervention period. CONCLUSIONS: The results suggest that the inclusion of FenuflakesTM, into regular dietary practices may effectively reduce glucose levels and enhance glycemic control in Asian Indian adults with type 2 diabetes.

AIM: This study aimed to evaluate the effectiveness of fenugreek as an adjuvant in managing oral potentially malignant disorders (OPMDs), specifically leukoplakia, lichen planus, and oral submucous fibrosis (OSMF). MATERIALS AND METHODS: Twenty-one participants prediagnosed with OPMDs were randomly divided into a study group (SG) and a control group (CG), with 10 participants in SG and 11 in CG, respectively. The SG received 2 gm of fenugreek as an adjuvant with standard systemic treatments tailored to the respective lesions: intralesional injection of vitamin A 1,00,000 IU (Aquasol A) and topical application of triamcinolone acetonide 0.1% (Kenacort) for 2 months for leukoplakia. Subjects with oral lichen planus were administered prednisolone 5 mg/day (Wysolone), chlorhexidine mouthwash 0.2% (Peridex), and Zincovit once daily for 8 weeks. For subjects with OSMF, one capsule of SM Fibro once daily for 12 weeks along with dexamethasone 1.5 mL (Decadron) was given, and hyaluronidase 1,500 IU (Hynidase) with 0.5 mL lignocaine HCL (Xylocaine) was injected intralesionally biweekly and mouth exercise was advised for 2 months; control group received only the standard treatment. Sociodemographic data were collected, and clinical assessments, evaluating size and shape for leukoplakia, erythema, and burning sensation for oral lichen planus, and mouth opening, cheek flexibility, and burning sensation for OSMF were assessed from baseline through 2 months. Data collected were organized in Excel and analyzed using Statistical Package for the Social Sciences version 21.0. RESULTS: The SG and CG had 10 and 11 participants, with 4 in each group for leukoplakia, 2 participants in SG and 3 in CG for lichen planus, and 4 participants for OSMF in each group, respectively. Most participants presented with leukoplakia under 2 cm on the buccal mucosa bilaterally, with no significant changes in size or shape postintervention. For lichen planus, mild erythema and burning sensation were noted, but there were no significant differences within or between groups postintervention. A mild burning sensation, a statistically significant improvement in mouth opening was observed in SG (p < 0.051)

The oleo-gum-resin of Boswellia serrata, an Ayurvedic herb for the treatment of chronic inflammatory diseases, contains both volatile (terpenes) and nonvolatile (boswellic acids) molecules as responsible for its bioactivity. The present randomized, double-blinded, placebo-controlled, crossover study evaluated the human pharmacokinetics of a 'natural' hybrid-hydrogel formulation of a unique full-spectrum boswellia extract (BFQ-20) (standardized for both volatile and nonvolatile bioactives) in comparison with unformulated extract (U-BE), for the first time. Mass spectrometry coupled with LC (UPLC-MS/MS) and gas chromatography (GC-MS/MS) measurements of the plasma concentration of boswellic acids and α-thujene at different post-administration time points followed by a single dose (400 mg) of U-BE and BFQ-20, to healthy volunteers (n = 16), offered 4-fold enhancement in the overall bioavailability of boswellic acids from BFQ-20, [area under the curve (AUC) (BFQ-20) = 9484.17 ± 767.82 ng * h/mL vs. AUC (U-BE) = 2365.87 ± 346.89 ng * h/mL], with the absorption maximum (Tmax) at 6.3 h post-administration and elimination half-life (T1/2) of 15.5 h (p < 0.001). While plasma α-thujene was not detectable upon U-BE administration, BFQ-20 provided significant absorption, [AUC (BFQ-20): 298.60 ± 35.48 ng * h/mL; Cmax: 68.80 ± 18.60 ng/mL; Tmax: 4.12 ± 0.38 h; T1/2: 16.24 ± 1.12 h]. Further investigation of the anti-inflammatory effect revealed 70.5% inhibition of paw edema in rats compared to 38.0% for U-BE. In summary, the natural self-emulsifying reversible hybrid-hydrogel (N'SERH) formulation of boswellia extract using fenugreek mucilage (FenuMat®) significantly increased the solubility (58-fold), stability, and bioavailability of both the volatile and non-volatile bioactives which in turn improved the anti-inflammatory efficacy of Boswellia extract.

Many aging men experience reduced energy and libido related to non-optimal testosterone levels. We conducted a randomized double-blind trial with TrigozimR fenugreek extract to assess impact on plasma and saliva testosterone, and some subjective effects. 95 men (40-80y) completed a 12-week intervention, taking 3 tablets daily with 0 mg (placebo; n = 22), 600 mg (n = 21), 1200 mg (n = 25) and1800 mg (n = 27) fenugreek extract and essential nutrients. Samples were collected at weeks 0, 2, 6, and 12. Participants answered a pre- and post-intervention questionnaire on lifestyle and libido. We measured total testosterone (HPLC-MS/MS) and sex hormone binding globulin (ELISA), calculated free testosterone index (FTI), and measured saliva testosterone. Plasma total testosterone and FTI increased after any dose of TrigozimR vs. baseline (13.0%, p = 1.0x10-4 and 16.3%, p = 6.2x10-6), but not vs. placebo (9.0%, p = 0.122 and 11.3% p = 0.059). 1800 mg TrigozimR resulted in 12.2% increased FTI (p = 0.025). Saliva testosterone concentration increased after any dose of TrigozimR vs. baseline (31.1%, p = 2.3x10-4) and vs. placebo (37.2%, p = 0.042). 1800 mg TrigozimR for 12 weeks resulted in 19.6% (p = 0.006) increased saliva testosterone. Compliance was confirmed by enhanced plasma concentration of 25-hydroxy vitamin D3. We observed no subjective effects or side-effects of TrigozimR. TrigozimR increased saliva and plasma testosterone concentration during intervention but only for saliva vs. placebo. Saliva may be preferred for measuring free testosterone due to no protein-bound testosterone. Copyright: © 2024 Lee-Ødegård et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

BACKGROUND: Trigonella foenum-graecum (Fenugreek) is an extensively researched phytotherapeutic for the management of Type 2 diabetes without any associated side effects. The major anti-diabetic bioactive constituents present in the plant are furostanolic saponins, which are more abundantly available in the seed of the plant. However, the bioavailability of these components depends on the method of extraction and hence formulation of the phytotherapeutic constitutes a critical step for its success. OBJECTIVE: The present study reports the efficacy of a novel, patented fenugreek seed extract, Fenfuro®, containing significant amount of furostanolic saponins, in an open-labelled, two-armed, single centric study on a group of 204 patients with Type 2 diabetes mellitus over a period of twelve consecutive weeks. RESULTS: Administration of Fenfuro® in the dosage of 500 mg twice daily along with metformin and/or sulfonylurea-based prescribed antidiabetic drug resulted in a reduction of post-prandial glucose by more than 33% along with significant reduction in fasting glucose, both of which were greater than what resulted for the patient group receiving only Metformin and/or Sulfonylurea therapy. Fenfuro® also resulted in reduction in mean baseline HOMA index from 4.27 to 3.765, indicating restoration of insulin sensitivity which was also supported by a significant decrease in serum insulin levels by >10% as well as slight reduction in the levels of C-peptide. However, in the case of the Metformin and/or Sulfonylurea group, insulin levels were found to increase by more than 14%, which clearly indicated that drug-induced suppression of glucose levels instead of restoration of glucose homeostasis. Administration of the formulation was also found to be free from any adverse side effects as there were no changes in hematological profile, liver function and renal function. CONCLUSION: The study demonstrated the promising potential of this novel phytotherapeutic, Fenfuro®, in long-term holistic management of type-2 diabetes.

BACKGROUND: Expensive lactation cookies (LCs) are marketed as milk boosters; however, their effectiveness remains unknown. OBJECTIVES: The objective of this study was to evaluate the effectiveness of the 1-mo daily intake of LCs on changes in objective and subjective milk production and breastfeeding self-efficacy. METHODS: This is a 1-mo, randomized controlled trial among 18-45-y-old exclusively lactating parents of healthy, term, 2-mo-old infants living in the United States from March to December 2021. Participants (n = 176) were randomly assigned to eat daily 56.5 g of either LCs with "galactagogues" (oatmeal, brewer's yeast, flax seeds, and fenugreek) or conventional cookies containing similar weight, calories, and presentation but lacking galactagogues. The primary outcome was baseline-to-1-mo changes in human milk production rate (HMPR), measured with a validated milk expression protocol. Secondary outcomes included changes in perceived insufficient milk (PIM) and lactation self-efficacy scores. RESULTS: Among 176 randomly assigned participants (age: 31.3 ± 5.8 y; 71.0% self-identified as White, 15.3% Hispanic/Latin, 6.3% Black, and 4.0% Asian), 90 participants (51.1%) completed endline HMPR measures and 129 (73.3%) completed secondary outcomes. Imputed models showed a mean increase in HMPR of 5.8 ± 15.7 mL/h in control participants and 5.5 ± 17.6 mL/h in the LC participants after 1 mo of daily intake of the cookie. No significant differences were observed with adjusted linear mixed models on the multiply imputed data comparing baseline-to-endline changes in HMPR, PIM, or breastfeeding self-efficacy: mean (SE) difference-in-differences for HMPR, -0.33 (4.97), P = 0.948; PIM scores (range: 5-50), -0.52 (1.83), P = 0.775; and self-efficacy scores (range: 14-70), 0.31 (2.23), P = 0.888, respectively. CONCLUSIONS: This study found no evidence for the effect of consuming LCs on HMPR, PIM, or breastfeeding self-efficacy in exclusively breastfeeding parents with an overall adequate perceived milk supply. Recommendations to consume LCs for increasing objective or subjective milk supply may deliver false hope and unnecessary financial costs at a vulnerable time. TR

Fisetin, a polyphenol found in several fruits and vegetables, has shown potential health benefits in many pre-clinical studies for neuroprotection, cardioprotection, chemoprevention, diabetes, inflammation and oxidative stress. However, the clinical effectiveness of fisetin may be limited by its poor bioavailability when ingested. Using a novel green technology of Hybrid-FENUMAT™, a food-grade fisetin formulation (FF-20) was developed through encapsulation of fisetin micelles into fenugreek galactomannan (FG) hydrogel scaffold to improve its physical characteristics and bioavailability. This is the first human pharmacokinetic study of fisetin following a single-dose, comparative, double-blinded, cross-over protocol, supplementing with FF-20 and unformulated fisetin (UF). Fifteen healthy volunteers were given a single dose of 1000 mg UF or 1000 mg FF-20 (delivering 192 mg fisetin) with a 10-d washout period between each dose. Blood samples were taken at 0⋅5, 1, 2, 3, 5, 8 and 12 h after both days of supplementation to quantify fisetin and geraldol, an active metabolite. The plasma concentration of fisetin when individuals consumed FF-20 was 26⋅9-fold greater than UF as determined by the area under the curve over 12 h [AUC0–12 h (FF-20) = 341⋅4 v. AUC0–12 h (UF) = 12⋅67]. The maximum plasma concentration (Cmax) was also more than twenty-three times higher when supplemented with FF-20 (238⋅2 ng/ml) compared to UF (9⋅97 ng/ml). The encapsulation also reduced the amount of conversion of fisetin to geraldol. No adverse events were reported during the study. Therefore, the encapsulation of fisetin into FG dietary fibre hydrogel scaffold could improve its delivery and bioavailability in human subjects. [Figure: see text]

The aim of the current randomized control trial (RCT) study was to investigate the effects of fenugreek seed extract on memory, depression, quality of life, blood pressure, and serum malondialdehyde (MDA) and total antioxidant capacity (TAC) levels in adult AD patients. This randomized clinical trial was conducted in geriatric homes in Iran. The study participants included 82 AD patients with mild-to-moderate memory deficit. Patients in the intervention group received 5 cc of fenugreek seed extract for 4 months and subjects in the control group received a placebo. Memory, depression, quality of life, and BP levels, as well as serum MDA and TAC, were assessed before and after the intervention. There was a significant increase in serum levels of TAC (p < 0.001) and a reduction in serum MDA status (p < 0.001) after 4 months of fenugreek seed extract supplementation. In addition, increasing levels of memory (p < 0.001) and quality of life (p < 0.001), as well as reduction of depression (p = 0.002), systolic BP (p < 0.001), and diastolic BP (p < 0.001) levels were detected in the intervention group compared with baseline. Fenugreek seed extract supplementation in AD patients shows promising positive effects on memory, quality of life, BP, and selective oxidative indices levels. © 2022 John Wiley & Sons, Ltd.

BACKGROUND: Herbs usually contain a mixture of biologically active constituents, which can interact with numerous prescribed drugs and alter their safety profiles. OBJECTIVES: The current investigation was aimed to evaluate the effect of commonly used herbal products including black seed (Nigella sativa), garden cress (Lepidium sativum), and fenugreek (Trigonella foenum-graecum) on the pharmacokinetics and pharmacodynamics of clopidogrel using a Wistar rat model. METHODS: A GC-MS analysis revealed the presence of several phytoconstitutents (polyphenols) in the extracts of black seed, garden cress, and fenugreek. These polyphenols have the potential to interfere with clopidogrel effect. Plasma concentrations of clopidogrel were measured at different time points in the absence and presence of the concurrent use of tested herbal products and the pharmacokinetic parameters were calculated. Bleeding time was measured in various groups as a measure of the antiplatelet effect of clopidogrel. RESULTS: Area under the plasma concentration-time curves (AUC0-∞) of clopidogrel were 35.53 ±0.89 μg/ml*h (p<0.05), 26.01 ±0.90 μg/ml*h (p>0.05) and 32.80 ±2.51 μg/ml*h (p<0.05) in the black seed, garden cress and fenugreek group, respectively, compared with that of the control group (27.02 ±0.42 μg/ml*h). Treatment with black seed also caused an increase in clopidogrel Cmax by 31.52% (p<0.05) and with fenugreek by 21.42% (p<0.05); Cmax, did not changed with garden cress treatment (6.48 ±0.15 μg/ml versus 6.12 ±0.21 μg/ml, p>0.05). The pharmacodynamic evaluation of the antiplatelet effect of clopidogrel in the presence of herbal products treatment showed a significant prolongation in the bleeding time from a control baseline by ~22-26%, and by added ~8-12% in reference to clopidogrel therapeutic effect (p<0.05). CONCLUSION: The concurrent use of black seed, fenugreek, or garden cress can alter the pharmacokinetics and pharmacodynamics of clopidogrel to varying degrees due to the presence of various bioactive polyphenols. This is probably due to changes in drug disposition and its antiplatelet action. Further confirmation can determine the clinical relevance of these observations an

CONTEXT: Garden cress (GC), fenugreek (FG), and black seed (BS) are traditional herbal medicine for managing hypertension. OBJECTIVE: The effects of the three herbs on the pharmacodynamics of metoprolol tartrate (MT) in hypertensive rats were investigated. MATERIALS AND METHODS: Wistar rats were divided in five groups (n = 6). Group I served as normal control group and Group II (hypertensive control group) had rats treated orally with N-nitro L-arginine methyl ester (L-NAME, 40 mg/kg/day) only. Groups III, IV, and V rats were orally treated with L-NAME (40 mg/kg/day) + GC (300 mg/kg, once daily), L-NAME (40 mg/kg/day) + FG (300 mg/kg, once daily) and L-NAME (40 mg/kg/day) + BS (300 mg/kg, once daily), respectively, for 2 weeks, and on the 14th day, blood pressure and heart rate were recorded using a tail-cuff blood pressure-measuring system. On the 16th day, a single dose of MT (10 mg/kg) was orally administered, and the rats' blood pressure and heart rate were recorded. RESULTS: GC, FG, and BS decreased systolic blood pressure (SBP) by 8.7%, 8.5%, and 8.7%, respectively, in hypertensive rats. A greater decrease in SBP by 14.5%, 14.8%, and 16.1% was observed when hypertensive rats were treated with L-NAME + GC + MT, L-NAME + FG + MT, and L-NAME + BS + MT, respectively. Similarly, hypertensive rats treated with the combination of herbs and MT had significantly lower diastolic blood pressure (DBP) than those treated with herbs alone and those treated with L-NAME alone. CONCLUSIONS: The combination of investigated herbs and MT had a beneficial effect on hypertension. However, the concurrent administration of drugs, particularly those predominantly cleared through CYP450 2D6-catalyzed metabolism, with the three investigated herbs should be considered with caution.

CONTEXT: Trigonella foenum-graecum L. (Fabaceae) has many therapeutic properties and anticancer potential. OBJECTIVE: The cytotoxic activities of standardized extracts and a fraction from fenugreek seeds and their compounds (sapogenins, flavone C-glycosides, alkaloid trigonelline) against human cancer SKOV-3, HeLa and MOLT-4 cells were evaluated. MATERIALS AND METHODS: Fenugreek seeds were extracted with 70% methanol (A) or water (B). Furthermore, the seeds were purified with petroleum ether and chloroform and next extracted with methanol to obtain fraction (C). The quantitative analysis of saponins and flavonoids in the extracts was done with HPLC methods. The extracts (5-120 µg/mL) and compounds (1-50 µg/mL) were tested on the cells by MTT assay and RTCA system. The effect of a fraction on ROS production, mitochondrial membrane potential and caspase-3/7 activity in HeLa and SKOV-3 cells was also evaluated by flow cytometry. RESULTS: The strongest cytotoxic activity on cancer cells showed the fraction C (IC50 was 3.91 ± 0.03 for HeLa, 3.97 ± 0.07 for SKOV-3, and 7.75 ± 0.37 for MOLT-4) with the highest content of steroidal saponins (163.18 ± 11.03 μg/mg) and flavone C-glycosides (820.18 ± 0.05 μg/mg). The fraction significantly increased ROS production (up to four times higher than in keratinocytes as control) and caspases activity in the cells. The examined flavonoids did not exhibit the cytotoxic activity in contrast to yamogenin, tigogenin, and diosgenin. CONCLUSIONS: The obtained results complement the data on the cytotoxic activity of Foenugraeci Semen and synergistic effect of flavonoids and saponins complex contained in the plant.

Commercial formulations of 29 commonly used herbal supplements (HSs) and grapefruit juice were evaluated for drug interaction potential via quantification of their CYP3A inhibitory potential in two in vitro experimental models of human small intestine, cryopreserved human intestinal mucosa (CHIM), and cryopreserved human enterocytes (CHEs). Two CYP3A substrates were used-in the studies with CHIM, CYP3A activity was quantified via liquid chromatography tandem mass spectrometry quantification of midazolam 1'-hydroxylation, whereas in CHE, luciferin-IPA metabolism to luciferin was quantified by luminescence. Upon treatment of CHIM with the estimated lumen concentration of the HS upon each oral administration (manufacturers' recommended dosage dissolved in 200 ml of culture medium), >80% CYP3A inhibition was observed for green tea extract, St. John's wort, valerian root, horehound, and grapefruit juice. Less than 50% inhibition was observed for fenugreek, aloe vera, guarana, soy isoflavone, maca, echinacea, spirulina, evening primrose, milk thistle, cranberry, red yeast rice, rhodiola, ginkgo biloba, turmeric, curcumin, white kidney bean, garlic, cinnamon, saw palmetto berries, panax ginseng, black elderberry, wheat grass juice, flaxseed oil, black cohosh, and ginger root. The results were confirmed in a a dose-response study with HSs obtained from three suppliers for the four inhibitory HSs (green tea extract, horehound, St. John's wort, valerian root) and three representative noninhibitory HSs (black cohosh, black elderberry, echinacea). Similar results were obtained with the inhibitory HSs in CHE. The results illustrate that CHIM and CHE represent physiologically relevant in vitro experimental models for the evaluation of drug interaction potential of herbal supplements. Based on the results, green tea extract, horehound, St. John's wort, and valerian root may cause drug interactions with orally administered drugs that are CYP3A substrates, as was observed for grapefruit juice. SIGNIFICANCE STATEMENT: In vitro evaluation of 29 popular herbal supplements in cryopreserved human intestinal mucosa identified green tea extract, horehound, St. John's wort, and valerian

Hydrogels can be used as bioactive dressings, which outperform traditional dressings and are widely used in wound hemostasis and healing. However, it is still a challenge to develop a hydrogel with good stability and strong mechanical properties for wound hemostasis and healing. Herein, we developed a novel composite polysaccharide hydrogel from fenugreek gum and cellulose. Fenugreek gum was combined with cellulose through hydrogen bonding to form a hydrogel to improve the mechanical properties of the composite hydrogel. The composite hydrogel had a porous structure, thermal stability, good water absorption and a sustained release effect. Furthermore, the composite hydrogel demonstrated good biocompatibility in vitro and in vivo. Notably, the superior performance of wound hemostasis and healing has been confirmed. Our results indicated that the composite hydrogel was a promising medical dressing and had the potential to promote wound healing.

BACKGROUND: The present article is related to in-vitro and in-vivo herb-drug interaction studies. OBJECTIVES: This study aimed to investigate the effect of Nigella sativa and fenugreek on the pharmacodynamics and pharmacokinetics of amlodipine. METHOD: Hypertensive rats of group-I were treated with amlodipine and rats of group-II and III were treated with N. sativa, and N. sativa + amlodipine and fenugreek, and fenugreek + amlodipine, respectively. Systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean blood pressure (MBP) of group-I, II and III rats were measured by the "tail-cuff system". RESULTS: N. sativa, as well as fenugreek, reduced the SBP, DBP and MBP. Simultaneously, administration of fenugreek + amlodipine or N. sativa + amlodipine showed better control of BP. Individually, fenugreek, as well as N. sativa, showed a surprising reduction in the heart rate. There was no remarkable effect of any of these two herbs on Cmax, AUC0-t, Kel, and terminal elimination half-life of amlodipine, but fenugreek altered the Tmax of amlodipine significantly, from 2 ± 1.2h in control to 7.2 ± 1.7h in fenugreek treated group, probably by delaying the absorption. CONCLUSION: Results of pharmacodynamics and pharmacokinetics studies suggested that simultaneous administration of fenugreek or N. sativa with amlodipine improved the pharmacological response of amlodipine in hypertensive rats, though there was no remarkable change in pharmacokinetic parameters (Cmax, Kel, elimination t1/2, and AUC0-t).

Hyperglycemia is one of the metabolic and homeostatic abnormalities that increase the cardiovascular mortality in diabetic patients by increased oxidative stress. We have recently reported amelioration of oxidative stress in cardiac tissue by dietary fenugreek (Trigonella foenum-graecum) seeds and onion (Allium cepa) in streptozotocin-induced diabetic rats. The mechanistic aspects of the cardio-protective influence of dietary fenugreek seeds (10%) and onion (3% powder) both individually and in combination on hyperglycemia-mediated cardiac damage was further investigated in this study on streptozotocin-induced diabetic rats. Cardio-protective influence of these dietary spices was evidenced by their blocking potential on renin-angiotensin system. This might be the consequence of reduced activation of angiotensin-converting enzyme (ACE) and angiotensin type 1 receptor (AT1) in cardiac tissue. The combination produced an additive effect on ACE and AT1 protein and mRNA expressions. Increased expression of type IV collagen, fibronectin, Bax, 4-hydroxynonenal, iNOS and metabolites of nitric oxide (nitrate/nitrite) along with disturbed PUFA-to-SFA ratio and activities of cardiac marker enzymes in blood confirmed the myocardial damage. Dietary fenugreek seed, onion and fenugreek + onion were found to ameliorate these pathological changes in the cardiovascular system. The beneficial effect being higher with the combination sometime amounting to additive (iNOS expression) or even a synergistic (cardiac Bax and type IV collagen expression and circulatory marker enzymes) in diabetic rats. Thus, the results of present investigation suggested that the combination of fenugreek seeds and onion offers higher beneficial influence in ameliorating cardiac damage accompanying diabetes.

INTRODUCTION: The use of complementary and alternative medicine (CAM) has been on the rise in recent years in the general population, as well as among patients with chronic diseases such as diabetes mellitus. The aim of this study was to add information regarding the use of CAM in patients with type 2 diabetes mellitus (DM2) in Israel and explore possible interactions between CAM and prescription medication (PM). METHODS: This is a cross-sectional study based on questionnaires. The study included type 2 diabetic patients who were hospitalized in an internal medicine department at Assaf Harofeh Medical Center, Zerifin, Israel, between December 2013 and December 2014. Possible interactions between CAM and PM were evaluated by a clinical pharmacist and a clinical pharmacologist. RESULTS: Out of 111 diabetic patients, 23.4% used CAM. There was no significant difference between the consumers and nonconsumers in terms of age, education, income, smoking, or alcohol habits. Only 11 of the 26 CAM consumers informed their physician regarding the use. We found possible drug-herb interactions in 19 of the 26 CAM consumers. A major interaction was found between omega-3 and antiaggregants and was encountered in 7 (26.9%) of the CAM consumers. Other minor and major interactions were found with vitamin E, ginkgo-biloba, co-enzyme Q10, green tea, fenugreek seeds, pyridoxine, and dandelion. CONCLUSIONS: Since CAM consumption is on the rise, it is desirable to improve our knowledge concerning their potential effects and adverse effects, especially in conjunction with PM. Given the complexity of pharmaceutics in patients with chronic diseases, among them patients with DM, the use of supplementary medicine cannot be ignored.

CONTEXT: Herb-drug interactions are a serious problem especially for drugs with a narrow therapeutic index, taking into consideration that herbal medicines are commonly used in various parts of the world. OBJECTIVE: The present study investigates the effect of fenugreek, garden cress, and black seed on the pharmacokinetics of theophylline in beagle dogs. MATERIALS AND METHODS: Beagle dogs received theophylline (200 mg) orally and blood samples were withdrawn at different time intervals (0.33, 0.66, 1.0, 1.5, 2, 3, 4, 6, 8, 12, 24, and 30 h). After a suitable washout period, each herb was given orally at doses of 25, 7.5, and 2.5 g, twice daily for 7 d. On the eighth day, theophylline was re-administrated orally and blood samples were collected. Plasma concentrations of theophylline were determined using HPLC and pharmacokinetic parameters were calculated using a non-compartmental analysis. RESULTS: Treatment with fenugreek (25 g, orally) lead to a decrease in Cmax and AUC0-t of theophylline of about 28% (p < 0.05) and 22% (p < 0.05), respectively, with no significant changes in T1/2λ compared with the baseline values. Garden cress caused a decrease in Cmax to a lesser extent and delayed Tmax of theophylline (2.10 ± 0.24 h versus 3.40 ± 0.74 h), while AUC0-∞ increased by 37.44%. No significant effect was observed for the black seed treatment on theophylline disposition as measured by Cmax, Tmax, AUC0-∞, and CL/F. DISCUSSION AND CONCLUSION: The concurrent use of fenugreek or garden cress alters theophylline pharmacokinetic behavior in an animal model. This could represent a modulation in cytochrome P450 activity, which is responsible for theophylline metabolism in beagle dogs. Further confirmation of these results in humans will warrant changes in theophylline dosing before the co-administration of such herbs.

OBJECTIVE: To provide pharmacists with practical information to guide consumers in their choices of herbal products and dietary supplements for the management of type 2 diabetes mellitus (T2DM) and its comorbid disease states. SUMMARY: The herbal and dietary supplement market has grown exponentially over the past decade as Americans increasingly use such agents for generalized health and the prevention and treatment of chronic disease states.1 Pharmacist advice is often requested on the use of these agents for the management of T2DM; however, this is an area that has insufficient evidence to support confident recommendations. Many published studies involving herbal agents and dietary supplements are small and poorly designed, with heterogeneous results. Pharmacists should be aware of the safety and efficacy data available for these agents, recognize potential drug interactions, and identify acceptable manufactured products. CONCLUSION: The strongest scientific evidence for blood glucose lowering effect is associated with alpha-lipoic acid and fenugreek. There is also good evidence supporting the use of ivy gourd, gymnema, and vitamin E for management of hyperglycemia; however, caution should be used when recommending vitamin E. Pharmacists should advise consumers to disclose use of any of these products to all of their health care providers.

Fenugreek is a widely used herbal medicine as a complementary therapy for diabetes mellitus. Lots of clinical trials have proved its beneficial effect on glycemic control parameters and lipid profiles. Thus, we conducted a systematic review and meta-analysis to evaluate the effectiveness and safety of fenugreek as a treatment for type 2 diabetes mellitus. We searched PubMed, Embase, Cochrane, China Knowledge Resource Integrated Database (CNKI), Korean studies Information Service System (KISS), Research Information Sharing Service (RISS), and ScienceON to select RCTs which used fenugreek targeting hyperglycemia with a control group. We used either a random effect model or a fixed model in a meta-analysis of Fasting blood glucose (FBG), 2 h plasma glucose during a 75 g oral glucose tolerance test (OGTT) (2-hPG), homeostatic model assessment for insulin resistance (HOMA-IR), glycosylated hemoglobin (HbA1c)/total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL-C), low density lipoprotein (LDL-C), body mass index (BMI). After screening, a total of 10 studies (706 participants) remained. Fenugreek significantly reduced FBG, 2-hPG, and HbA1c, but it did not significantly decrease HOMA-IR. Moreover, it significantly improved TC, TG, and HDL-C, while there were no significant differences in LDL-C and BMI. Hepatic or renal toxicity was not observed, and there were no severe adverse events associated with fenugreek despite mild gastrointestinal side effects in some studies. In conclusion, fenugreek improves overall glycemic control parameters and lipid profile safely.