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New meta-analyses, RCTs and systematic reviews that we monitor daily in PubMed. Independently indexed, not editorially curated.
Complementary therapies in medicine · 2021
This study investigated the effect of French maritime pine bark extract (PBE) supplementation on metabolic parameters, vascular cell adhesion molecule 1 (VCAM-1), urinary albumin-to-creatinine ratio (UACR), and anthropometric indexes in patients with type 2 diabetes (T2DM) and microalbuminuria. This randomized, double-blind, placebo-controlled clinical trial was conducted on 46 patients with T2DM and the evidence of microalbuminuria aged 30-65 years. Patients were recruited from the endocrinology clinic of Sina hospital (Tabriz, Iran) from March 2018 to April 2019. The subjects were randomly assigned to receive two capsules/day each containing 50mg of PBE or placebo for eight weeks. Glycemic parameters, serum VCAM-1 and lipid profile, UACR, and anthropometric indexes were measured for all patients at baseline and the end of the study. PBE supplementation significantly reduced glycosylated hemoglobin, VCAM-1, total cholesterol, UACR, waist circumference, and waist-to-height ratio compared to the placebo group at the end of the study (all P < 0.05). Changes in fasting blood glucose, insulin, triglyceride, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were not significant between the two groups (all P > 0.05). The study findings demonstrated some favorable effects of PBE supplementation on glycemic control, serum VCAM-1 and total cholesterol levels, and microalbuminuria, as well as abdominal obesity in patients with T2DM.
Osteoarthritis and cartilage · 2021
The RADIANT study aimed to investigate the efficacy and safety of a complementary medicine supplement combination in people with hand osteoarthritis (HOA). This was an internet-based, double-blind, randomised, placebo-controlled trial. Participants aged over 40 years with symptomatic HOA with radiographic confirmation (Kellgren Lawrence grade ≥ 2) throughout Australia were recruited and randomly assigned (1:1) to receive either a supplement combination composed of Boswellia serrata extract 250 mg/day, pine bark extract 100 mg/day, methylsulfonylmethane 1,500 mg/day and curcumin 168 mg/day or placebo for 12 weeks. The primary outcome was change in hand pain assessed using a visual analogue scale (VAS 0-100) from baseline to week 12. A range of secondary outcomes and additional measures were recorded. Adverse events were monitored weekly. One hundred and six participants were included with mean age 65.6 years and 81% were women. 45% of the participants were graded as KLG 4, 40% KLG three and 39 (37%) had erosive OA. There was no significant difference in pain VAS reduction between groups. The adjusted between group difference in means (95%CI) was 5.34 (-2.39 to 13.07). Five participants (10%) in the supplement combination group discontinued study treatment due to AE vs four participants (7%) in the placebo group. There were no significant differences in symptomatic relief between the two groups over 12 weeks. These findings do not support the use of the supplement combination for treating hand pain in people with HOA. Prospectively registered (Australian New Zealand Clinical Trials Registry ACTRN12619000835145, 31/05/2019).
Skin pharmacology and physiology · 2021
Oral supplementation with a standardized extract from the bark of the French pine (Pycnogenol®) has been reported to benefit the skin. It might thus represent an easy-to-use strategy to improve the skin health of individuals who are exposed to considerable environmental stress in large urban areas. We investigated if oral intake of Pycnogenol® can benefit the skin of Han Chinese working outdoors in Beijing, China. In a monocentre, double-blind, randomized, placebo-controlled, and crossover study, the effects of Pycnogenol® intake (2 × 50 mg/day for a total of 12 weeks) on a variety of skin physiological parameters was studied in Chinese subjects (n = 76), from spring to autumn, who were working outdoors in Beijing, China. During the intervention period, study subjects were constantly exposed to increased levels of particulate matter (PM)2.5 as well as seasonal changes in humidity and temperature. Despite this environmental stress, Pycnogenol® intake prevented (i) a decrease in the skin hydration, (ii) transepidermal water loss (TEWL), and (iii) skin darkening during the dry autumn season. In addition, Pycnogenol® intake improved (iv) viscoelastic skin properties such as gross elasticity and elastic recovery irrespective of the season. These beneficial effects were not observed if the same subjects were supplemented with placebo. Oral intake of Pycnogenol® benefits the skin in Han Chinese, who are working outdoors under considerable environmental stress.
International journal of environmental research and public health · 2021
This report is part of a larger study designed to rapidly and efficiently screen potential treatments for Gulf War Illness (GWI) by testing nine different botanicals. In this placebo-controlled, pseudo-randomized, crossover clinical trial of 20 men with GWI, we tested three botanical agents with putative peripheral and central anti-inflammatory actions: curcumin (Curcuma longa), boswellia (Boswellia serrata), and French maritime pine bark extract (Pinus pinaster). Participants completed 30 +/- 3 days of baseline symptom reports, followed by 30 +/- 3 days of placebo, 30 +/- 3 days of lower-dose botanical, and 30 +/- 3 days of higher-dose botanical. Participants then repeated the process with a new botanical until completing up to three botanical cycles. Data were analyzed using linear mixed models. Curcumin reduced GWI symptom severity significantly more than placebo at both the lower (p < 0.0001) and higher (p = 0.0003) dosages. Boswellia was not more effective than placebo at reducing GWI symptoms at either the lower (p = 0.726) or higher (p = 0.869) dosages. Maritime pine was not more effective than placebo at the lower dosage (p = 0.954) but was more effective than placebo at the higher dosage (p = 0.006). This study provides preliminary evidence that curcumin and maritime pine may help alleviate symptoms of GWI. As a screening study, a final determination of the efficacy of these compounds for all individuals with GWI cannot be made, and further studies will need to be conducted to determine strength and durability of effects, as well as optimal dosage. These results suggest that GWI may, at least in part, involve systemic inflammatory processes. This trial was registered on ClinicalTrials.gov (NCT02909686) on 13 September 2016.
Phytotherapy research : PTR · 2021
Inflammation plays an important role in the pathophysiology of traumatic brain injury (TBI). Based on the anti-inflammatory properties of French maritime pine bark extract and the neuroprotective effects, we aimed to evaluate the effects of its supplementation on TBI. Sixty-seven TBI patients admitted to the intensive care units (ICUs) were enrolled. After stabilizing the hemodynamic status, the intervention group received 150 mg of French maritime pine bark extract supplementation (Oligopin) with enteral nutrition for 10 days. The control group received a placebo. Inflammatory status and oxidative stress markers were measured three times. Also, clinical and nutritional statuses were assessed. Supplementation, significantly decreased IL-6 (β = -53.43 pg/ml, 95% confidence interval [CI] = -91.74, -15.13, p = .006), IL-1β (β = -111.66 pg/ml, 95% CI = -183.79, -39.5402, p = .002) and C-reactive protein (β = -19.99 mg/L, 95% CI = -27.23, -12.76, p ˃ .001) in the intervention group compared to control group after 10 days. Clinical scores including acute physiology and chronic health evaluation II and sequential organ failure assessment were reduced (β = -3.72, 95% CI = -5.96, -1.49, p = .001and β = -2.07, 95% CI = -3.23, -0.90, p < .001, respectively), and Nutric score was reduced compared to control group (β = -.60, 95% CI = -1.08, -0.12, p = .01). The survival rate was higher by 15% in the intervention group compared to control group. Oligopin supplementation in TBI patients in ICU reduced inflammation and improved the clinical status and malnutrition score and thereby reducing the mortality rate.
Complementary therapies in medicine · 2022
High blood pressure (BP) is a major risk factor for cardiovascular disease and prevalence rates continue to rise with ageing populations. Polypharmacy remains a burden among the ageing, thus alternative effective strategies are warranted. This study investigated the effects of a polyphenols rich dietary supplement containing Pinus massoniana bark extract (PMBE) for modulating BP in healthy Australian adults. This study is a secondary analysis of data from a double-blinded, placebo-controlled clinical trial. Sixty-two healthy adults aged 55-75 years were randomized to receive 50 mL dietary supplement containing placebo (0 mg PMBE) or PMBE (1322 mg PMBE) daily for 12 weeks. Seated systolic BP (SBP) and diastolic (DBP) were measured at baseline, 6 weeks and 12 weeks. Effects of PMBE on modulating BP was also explored in this study stratified for SBP status (optimal v high) as well as by SBP medication status. Mixed effect regression modelling was employed involving fixed categorical effects for elapsed time, treatment assignment and their interaction as well as random subject-level intercept to account for within-subject correlations resulting from repeated measurements. Significant models were further examined by addition of covariates and power calculations were performed since this study was a secondary analysis. SBP significantly reduced (-3.29 mmHg, p = 0.028) after PMBE at 12 weeks compared to baseline. SBP in individuals with normal-high SBP (>120 mmHg) in the PMBE group reduced by - 6.46 mmHg (p = 0.001) at 12 weeks compared to baseline. No significant changes were reported for individuals with optimal (≤120 mmHg) SBP nor did DBP significantly change in either study groups. In individuals with non-medicated normal-high SBP, SBP significantly reduced by - 7.49 mmHg (p = 0.001) and DBP by - 3.06 mmHg (p = 0.011) at 12 weeks compared to baseline after PMBE. Cross-group comparisons were not statistically different. A polyphenol-rich dietary supplement derived from PMBE led to a clinically and statistically significant reduction in SBP in adults. Future studies to investigate the effects of PMBE-polyphenol supplementation on BP are warranted to confirm and explore optimal dose and impact on hypertension.
Complementary medicine research · 2023
Turpentine-containing substances are considered effective in treating cutaneous bacterial infections, but reliable clinical data are scant. We investigated the efficacy and safety of an ointment containing larch turpentine (from Larix decidua), eucalyptus oil (from Eucalyptus globulus), and turpentine oil (from Pinus pinaster) in outpatients with painful skin abscesses in a randomized, placebo-controlled, double-blind study. 116 outpatients with skin abscesses used verum or placebo for 10 days. Sum score of the patient's discomforts, changes in abscess size, rate of therapeutic success, and complete healing served as outcome parameters. Fifty-four patients were treated with verum and 56 with placebo. According to the patient's discomfort sum score, patients in the verum group showed a better improvement compared to the placebo group (7.3 vs. 4.7; p = 0.024), and subjective assessment by the investigators revealed a higher treatment success rate after verum (70% vs. 48%; p = 0.021). Complete healing was documented in 67% of the patients receiving verum versus 46% in the placebo group (p = 0.037). There was a positive trend toward a larger decrease in the abscess sizes in the verum group compared to the placebo group (p = 0.07). The ointment studied is an effective and safe option for the treatment of bacterial skin diseases. Hintergrund: Terpentinhaltige Substanzen werden in der Behandlung von bakteriellen Hauterkrankungen als effektiv betrachtet, aber bis jetzt ist die klinische Datenlage noch ungenügend. Ziel: Wir haben hier die Wirksamkeit und Sicherheit einer terpentinhaltigen Salbe mit den Inhaltstoffen Lärchenterpentin (von Larix decidua), Eukalptusöl (von Eucalyptus globulus) und Terpentinöl (von Pinus pinaster) in einer randomisierten, Placebo-kontrollierten, doppel-blind Studie in der Behandlung von ambulanten Patienten mit schmerzhaften Hautabszessen untersucht. Intervention: 116 ambulante Patienten mit Hautabs­zessen haben entweder Verum oder Placebo für 10 Tage angewendet. Ermittelt wurde als Ergebnis die Summenzahl der Beschwerden, die Änderung der Abszessgröße, die therapeutische Erfolgsrate und die komplette Heilung der Patienten. Ergebnis: 54 Patienten wurden mit Verum und 56 mit Placebo behandelt. Laut der Summenzahl der Beschwerden zeigten die Patienten der Verumgruppe eine Verbesserung im Vergleich zur Placebogruppe (7.3 vs. 4.7; p = 0.024), des Weiteren zeigte die subjektive Wahrnehmung der Prüfärzte einen höheren Behandlungs­erfolg nach der Verumgabe (70% vs. 48%; p = 0.021). Eine komplette Heilung wurde bei 67% der Verum gegenüber 46% der Placebogruppe beobachtet (p = 0.037). Außerdem war ein positiver Trend in Bezug auf die Reduktion der Abszessgröße in der Verumgruppe gegenüber der Placebogruppe zu sehen (p = 0.07). Schlussfolgerung: Die untersuchte Salbe ist eine wirksame, effektive und sichere Behandlungsoption bei bakteriellen Hauterkrankungen.
Frontiers in endocrinology · 2023
The objective of this meta-analysis was to review clinical trials of the combination of Pycnogenol ® and L-arginine (PAL) in the treatment of erectile dysfunction in men and to observe the effect of PAL combined therapy on sexual function in patients with erectile dysfunction (ED), and we hope to provide more choices of drugs for treating patients with ED. The study was constructed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. We searched seven databases from inception to 15 February 2023, for a comprehensive search of clinical trials using relevant keywords. Continuous variables in this meta-analysis were calculated using the mean difference and 95% confidence interval. All relevant statistical analyses were performed using RevMan v. 5.4 software. Three studies with 184 patients were included in the present meta-analysis. There were no significant differences in the basic characteristics of the included studies. The results of the current meta-analysis showed that there were significant differences in the international index of erectile function scores (erectile domain), intercourse satisfaction scores, orgasmic function scores, overall satisfaction scores, and sexual desire scores between the combination treatment group and the control group. There was no significant difference in improving the testosterone levels between the two groups. These results indicate that the combination of PAL may have a significant effect on improving sexual function in patients with mild to moderate ED. This study will provide clinicians with more options for treating patients with ED. More randomized controlled trials are needed in the future to further demonstrate the effect of combination therapy on sexual function in patients with ED. https://www.crd.york.ac.uk/PROSPERO/#myprosperoUnique, Identifier: CRD42023411781.
Skin pharmacology and physiology · 2023
Folliculitis is a painful infection and inflammation of the hair follicles, mostly caused by bacterial, fungal, or, more rarely, viral infections. Turpentine derivatives have been used traditionally to treat various skin infections and could thus also be effective in treating folliculitis. We carried out an open, prospective, randomized, placebo- and comparator-controlled multicenter trial to evaluate the efficacy and safety of an ointment containing pine turpentine oil, larch turpentine, and eucalyptus oil in the treatment of acute folliculitis. Seventy outpatients with acute folliculitis were treated with the turpentine ointment, a comparator (povidone iodine solution), or a placebo (Vaseline) for 7 days. Photographs of the affected skin areas were taken by the physicians at four visits and by the patients on a daily basis. Photographs were evaluated by blinded observers. Primary efficacy endpoint was the change in total hair follicle lesion counts. Secondary endpoints included the evolution of the lesion counts in the course of the study, responder rate (improvement of follicle lesions by at least one count), and the patient's global assessment. Safety endpoints were the tolerability of the treatments and adverse event recording. A decrease of follicle lesions counts was detected for both active treatments but not for placebo, but the differences among groups were not statistically significant. As for the secondary endpoints, the ointment showed statistically significant superiority over placebo for the evolution of the lesions during the course of the study (p = 0.017), the responder rate (p = 0.032), and the subjective efficacy assessment by patients (p = 0.029). All treatments were equally well tolerated, with a similar number of treatment-emergent adverse events. The turpentine ointment is an effective and safe option for the treatment of folliculitis.
BMC complementary medicine and therapies · 2025
Supplementation with pine bark extract (PBE) may improve risk factors associated with cardiometabolic syndrome (CMS). The effects of PBE supplementation on cardiometabolic risk factors were evaluated in this systematic review and meta-analysis of randomized controlled trials (RCTs). A comprehensive search of various databases was performed to identify relevant RCTs published up to September 2024. A random-effects model was employed for the meta-analysis, which included 27 RCTs with 1,685 participants. The findings indicated that PBE supplementation significantly reduced systolic blood pressure (SBP) (weighted mean difference (WMD): -2.26 mmHg, 95% confidence interval (CI): -3.73, -0.79; P = 0.003), diastolic blood pressure (DBP) (WMD: -2.62 mmHg, 95% CI: -3.71, -1.53; P < 0.001), fasting blood sugar (FBS) (WMD: -6.25 mg/dL, 95% CI: -9.97, -2.53; P = 0.001), hemoglobin A1c (HbA1c) (WMD: -0.32%, 95% CI: -0.54, -0.11; P = 0.003), body weight (WMD: -1.37 kg, 95% CI: -1.86, -0.88; P < 0.001), and low-density lipoprotein (LDL) cholesterol (WMD: -5.07 mg/dL, 95% CI: -9.21, -0.94; P = 0.016) in the PBE-treated group compared to their untreated counterparts. However, no significant impact of PBE was observed on waist-to-hip ratio (WHR), body mass index (BMI), waist circumference (WC), or serum levels of insulin, high-density lipoprotein (HDL) cholesterol, triglycerides (TG), and total cholesterol (TC). Supplementation with PBE may ameliorate specific cardiometabolic risk factors, as indicated by reductions in body weight, DBP, SBP, FBS, LDL, and HbA1c levels. This approach can be regarded as an adjunct therapeutic strategy for CMS management. Further high-quality trials with larger sample sizes and longer durations are required to validate these findings.
Nutrients · 2025
Background: Gingival inflammation is highly prevalent and may impact systemic health. While professional mechanical plaque removal (PMPR) is the standard treatment, dietary interventions may provide additional benefits. The French maritime pine bark extract Pycnogenol® has anti-inflammatory and antioxidant properties, but its impact on inflammatory biomarkers in saliva and serum has not been studied in a controlled clinical trial. Methods: In this randomized, double-blind, placebo-controlled clinical trial, 91 participants received Pycnogenol® (100 mg twice daily; n = 46) or a placebo (n = 45) following PMPR. Saliva and serum samples were collected at baseline, and after two and three months. Inflammatory biomarkers (IL-1β, IL-6, MMP-8, and MMP-9) and polyphenol concentrations were analyzed using ELISA and LC-MS/MS. Results: Pycnogenol® supplementation significantly reduced salivary MMP-8 levels (p = 0.0261), and serum IL-6 levels compared to placebo (p = 0.0409). Additionally, ferulic acid, caffeic acid, and the gut microbial metabolite 5-(3,4-dihydroxyphenyl)-γ-valerolactone (M1) significantly increased in saliva following Pycnogenol® intake. A correlation analysis revealed a significant inverse association between bleeding on probing and M1 concentration in saliva (r = -0.3476, p = 0.0167). Conclusions: Dietary supplementation with Pycnogenol® significantly reduced key inflammatory biomarkers and increased polyphenol concentrations in saliva, suggesting a potential anti-inflammatory effect of Pycnogenol® on gingival inflammation. Trial registration: ClinicalTrials.gov (NCT05786820).
Nutrients · 2025
The New Zealand pine bark has been demonstrated in vitro to inhibit digestive enzymes involved in carbohydrate digestion (alpha-amylase, alpha-glucosidase, and dipeptidyl-peptidase 4 (DPP-4)). This study aims to investigate the inhibitory effects of the New Zealand pine bark on sucrose uptake and glycaemic responses in humans. A single-blind, randomised, placebo-controlled, crossover trial was carried out involving healthy adults (n = 40 (M: 12, F: 28), 30.1 ± 1.3 years, BMI 23.4 ± 0.5 kg/m2, HbA1c 32.5 ± 0.6 mmol/mol, FBG 4.7 ± 0.1 mmol/L). A control (75 g of sucrose powder only), and two doses of the pine bark extract (50 and 400 mg) were provided on separate occasions, with 75 g of sucrose mixed in 250 mL of water. Blood samples were collected at -10, 0, 15, 30, 45, 60, 90, and 120 min via a finger prick test. A linear mixed model for repeated measures (SPSS v30, IBM) was applied, and data presented as model-adjusted mean ± SEM. Compared to control (247.5 ± 14.0 mmol/L⋅min), the iAUCglucose was significantly reduced with the 400 mg dose (211.8 ± 13.9 mmol/L⋅min, 14.4% reduction, and p = 0.037), but not with 50 mg dose (220.8 ± 14.2 mmol/L⋅min, 10.8% reduction, and p = 0.184). Compared to control (9.1 ± 0.2 mmol/L), glucose peak value was significantly reduced with the 50 mg dose (8.6 ± 0.2 mmol/L, 5.5% reduction, and p = 0.016) but not with the 400 mg dose (8.7 ± 0.2 mmol/L, 4.4% reduction, and p = 0.093). There were no statistically significant changes in postprandial insulin levels with the pine bark extract compared to control. The New Zealand pine bark extract attenuated sucrose uptake with improved glycaemic responses, and may therefore be useful as a hypoglycaemic adjunct to the diet.
Actas urologicas espanolas · 2025
To determine the effectiveness and safety of pharmacological therapy in men older than 18 years with primary or secondary anorgasmia in terms of induced orgasm, improvement of the International Index of Erectile Function (IIEF), or Arizona Sexual Experience Scale (ASEX). we conducted this systematic review according to the recommendations of the Cochrane Collaboration and following the PRISMA Statement. We designed a search strategy in MEDLINE (OVID), EMBASE, LILACS, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to the present. We assessed the risk of bias based on the STROBE statement for observational studies and the Rob 2.0 tool for clinical trials. 234 patients were included, and 232 were treated with pharmacological therapy in seven studies. Some pathologies reported were a history of prostatectomy, hypogonadism, psychiatric disorders, and use of antidepressants. Cabergoline was the most frequently administered treatment, followed by yohimbine and bupropion. The cabergoline improved orgasm in 66% of the population and yohimbine in 55%. The change in IIEF orgasmic function improved significantly with cabergoline and bupropion (P = <0.001 and P = 0.002). The ASEX improved with pycnogenol and was maintained in months 2,3 and 4 (p ≤ 0.05). The side effects reported were mild in three studies. Amantadine required discontinuation due to depression. Pharmacological therapy with cabergoline, yohimbine, bupropion, and pycnogenol can have a positive effect on the orgasmic function of patients with primary or secondary anorgasmia.
BMC complementary medicine and therapies · 2025
The global prevalence of diabetes is increasing rapidly. While glycaemic control remains the cornerstone of type 2 diabetes (T2DM) management, hypoglycaemic medications are associated with side effects. Many individuals with T2DM use herbal medicines despite potential risks. This review aims to comprehensively evaluate the efficacy and safety of herbal medicines for T2DM. Four electronic databases were searched from August 2018-August 2023 for umbrella reviews, meta-analyses, and systematic reviews on herbal medicine for T2DM. The primary outcome was glycaemic control assessed by glycated haemoglobin (HbA1c); secondary outcomes included measures of insulin resistance, quality of life and adverse events. Quality assessment was performed using A Measurement Tool to Assess Systematic Reviews Version 2 (AMSTAR 2) and certainty of evidence for the primary outcome was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Eight meta-analyses and two systematic reviews were included. Ginger, turmeric, and Jinlida granules significantly decreased HbA1c compared to placebo (mean differences (MD): -0.467%, -0.486%, -0.283%, respectively) with moderate to high certainty evidence. Berberis vulgaris, Gegen Qinlian decoction and pycnogenol may potentially decrease HbA1c (very low certainty evidence). Ginger, turmeric, cardamom, Berberis vulgaris, Nigella sativa, and various Chinese herbal medicines demonstrated improvements in insulin resistance measures. However, overall confidence in these findings is limited due to the low to very low quality of the included reviews. Few mild adverse effects were reported, but data was incomplete. Current evidence supports the use of ginger and turmeric for glycaemic control in type 2 diabetes, however, given the high clinical heterogeneity and low quality of the review, our confidence in this finding is somewhat limited. Herbal medicines should be used only as an adjunct to conventional treatment, with shared decision-making between clinicians and patients. Careful monitoring for hypoglycaemia is essential, particularly when herbal medicines are used concurrently with antidiabetic drugs, given a current lack of data on herb-drug interactions. Future research should clarify optimal regimens, safety profiles, and include diverse populations to enhance generalisability.
Phytotherapy research : PTR · 2022
The plants Rutaceae family are known to have contributed a lot toward food and medicine. The most important metabolites of the family are flavonoids. A systematic review was conducted to collect chemical and pharmacological information of flavonoids isolated from family Rutaceae till 2018. A plethora of flavonoids have been isolated and studied systematically for various bioactivities, including anticancer, antibacterial, antiviral, analgesic, antioxidant, antidiabetic, antiinflammatory, in bronchitis, ulcers, and so on. The important groups of flavonoids isolated are naringin, poncirin, rhoifolin, marmesin, hesperidin, tangeretin, nobiletin, glychalcone, glyflavanone, lemairone, acacetin 3,6-di-C-glucoside, vicenin-2, lucenin-2 4'-methyl ether, narirutin 4'-O-glucoside, apigenin 8-C-neohesperidoside, phloretin 3',5'-di-C-glucoside, rutin, rhamnetin, dihydrokaempferol, dihydrokaempferol 3-O-rhamnoside (engeletin) and kaempferol, excavaside A and B, myricetin 3-O-β-D-rutinoside, myricetin 3,3'-di-α-l-rhamnopyranoside, myricetin 3'-α-l-rhamnopyranoside, and others. The flavonoids isolated from the citrus family need to be considered from a nutraceutical, therapeutic, and pharmaceutical point of view for future medicine.
Thrombosis and haemostasis · 2022
Cardiovascular disease, in particular due to arterial thrombosis, is a leading cause of mortality and morbidity, with crucial roles of platelets in thrombus formation. For multiple plant-derived phytochemicals found in common dietary components, claims have been made regarding cardiovascular health and antiplatelet activities. Here we present a systematic overview of the published effects of common phytochemicals, applied in vitro or in nutritional intervention studies, on agonist-induced platelet activation properties and platelet signaling pathways. Comparing the phytochemical effects per structural class, we included general phenols: curcuminoids (e.g., curcumin), lignans (honokiol, silybin), phenolic acids (caffeic and chlorogenic acid), derivatives of these (shikimic acid), and stilbenoids (isorhapontigenin, resveratrol). Furthermore, we evaluated the flavonoid polyphenols, including anthocyanidins (delphinidin, malvidin), flavan-3-ols (catechins), flavanones (hesperidin), flavones (apigenin, nobiletin), flavonols (kaempferol, myricetin, quercetin), and isoflavones (daidzein, genistein); and terpenoids including carotenes and limonene; and finally miscellaneous compounds like betalains, indoles, organosulfides (diallyl trisulfide), and phytosterols. We furthermore discuss the implications for selected phytochemicals to interfere in thrombosis and hemostasis, indicating their possible clinical relevance. Lastly, we provide guidance on which compounds are of interest for further platelet-related research.
The Science of the total environment · 2022
Biopesticides obtained from renewable resources and associated with biodegradability have the potential to address resource limitations and environmental pollution, often caused by many conventional pesticides, due to the facility of natural products to run in natural nutrient cycles. Flavonoids are considered benign substitutes for pesticides, however, little comprehensive information of their pesticidal activities and critical evaluation of their associated advantages is available. Therefore, this systematic review assessed sources, structures, activities and the environmental fate of flavonoids on a basis of 201 selected publications. We identified 281 different flavonoids that were investigated for their pesticidal activity as either a pure compound or a flavonoid-containing extract, with quercetin, kaempferol, apigenin, luteolin and their glycosides as the most studied compounds. Agricultural or food waste, a potential sustainable source for flavonoids, represent 10.6% of the plant sources of flavonoids within these studies, showing the currently underutilization of these preferable feedstocks. Analysis of pesticidal activities and target organisms revealed a broad target spectrum for the class of flavonoids, including fungi, insects, plants, bacteria, algae, nematodes, molluscs and barnacles. Little information is available on the environmental fate and biodegradation of flavonoids, and a connection to studies investigating pesticidal activities is largely missing. Emerging from these findings is the need for comprehensive understanding of flavonoids pesticidal activities with emphasis on structural features that influence activity and target specificity to avoid risks for non-target organisms. Only if the target spectrum and environmental fate of a potential biopesticide are known it can serve as a benign substitute. Then, flavonoids can be integrated in a valorization process of agricultural and food waste shifting the extract-produce-consume linear chain to a more circular economy.
Frontiers in pharmacology · 2022
Beginning from December 2019, widespread COVID-19 has caused huge financial misfortunes and exceptional wellbeing emergencies across the globe. Discovering an effective and safe drug candidate for the treatment of COVID-19 and its associated symptoms became an urgent global demand, especially due to restricted information that has been discharged with respect to vaccine efficacy and safety in humans. Reviewing the recent research, olive leaves were selected as a potential co-therapy supplement for the treatment and improvement of clinical manifestations in COVID-19 patients. Olive leaves were reported to be rich in phenolic compounds such as oleuropein, hydroxytyrosol, verbascoside, apigenin-7-O-glucoside, and luteolin-7-O-glucoside and also triterpenoids such as maslinic, ursolic, and oleanolic acids that have been reported as anti-SARS-CoV-2 metabolites in recent computational and in vitro studies. In addition, olive leaf extract was previously reported in several in vivo studies for its anti-inflammatory, analgesic, antipyretic, immunomodulatory, and antithrombotic activities which are of great benefit in the control of associated inflammatory cytokine storm and disseminated intravascular coagulation in COVID-19 patients. In conclusion, the described biological activities of olive leaves alongside their biosafety, availability, and low price make them a potential candidate drug or supplement to control COVID-19 infection and are recommended for clinical investigation.
Inflammopharmacology · 2022
Apigenin is a member of the flavonoid family that can regulate various biological processes, which is characterized as a treatment of different inflammatory disorders and pathological problems associated with oxidative stress (OS). Recent research has focused on apigenin immunomodulatory properties as a potential treatment for different types of lung injuries. This meta-analysis was designed to determine the impact of apigenin treatment on inflammatory markers and OS parameters in animal models of lung injuries. The comprehensive literature search was conducted using electronic databases such as Google Scholar, PubMed, Web of Science, Scopus, and Embase up to August 2021. To assess apigenin's effect on inflammatory mediators and OS biomarkers in lung injury animal models, we used the I2 statistic to determine the heterogeneity. We then pooled data as standardized mean difference (SMD) with a 95% confidence interval (CI). Our meta-analysis of the pooled data for inflammatory biomarkers demonstrated that the apigenin administration significantly decreased the NF-κB expression (SMD - 1.60, 95% CI [- 2.93 to - 0.26]; I2 = 89.0%, p < 0.001), IL-1β (SMD - 4.30, 95% CI [- 6.24 to - 2.37]; I2 = 67.3%, p = 0.047), IL-6 (SMD - 4.10, 95% CI [- 5.04 to - 3.16]; I2 = 72.6%, p < 0.001), TNF-α (SMD - 3.74, 95% CI [- 4.67 to - 2.82]; I2 = 84.1%, p < 0.001), and TNF-α gene expression (SMD - 3.44, 95% CI [- 4.44 to - 2.43]; I2 = 0.0%, p = 0.622). This study also indicated the efficacy of apigenin in increasing the level of CAT (SMD 4.56, 95% CI [3.57 to 5.55]; I2 = 15.3%, p = 3.15), GSH (SMD 5.12, 95% CI [3.53 to 6.70]; I2 = 77.6%, p < 0.001), and SOD (SMD 3.45, 95% CI [2.50 to 4.40]; I2 = 79.2%, p < 0.001), and decreasing the level of MDA (SMD - 3.87, 95% CI [- 5.25 to - 2.49]; I2 = 80.3%, p < 0.001) and MPO (SMD - 4.02, 95% CI [- 5.64 to - 2.40]; I2 = 88.9%, p < 0.001), TGF- β (SMD - 3.81, 95% CI [- 4.91 to - 2.70]; I2 = 73.4%, p = 0.001) and W/D level (SMD - 3.22, 95% CI [- 4.47 to - 1.97]; I2 = 82.1%, p < 0.001) than control groups. Overall, our findings showed the immunomodulatory potential of apigenin as an alternative treatment for the suppression of inflammatory responses and OS in different types of lung injury diseases. Nevertheless, due to the paucity of clinical studies, reliable preclinical models, and clinical settings, evaluating the influence of apigenin on lung injury is required in the future. Before conducting large-scale clinical trials, detailed human pharmacokinetic studies are also needed to establish dosage ranges and determine the initial safety and tolerability of apigenin.
Critical reviews in oncology/hematology · 2022
Apigenin is being increasingly recognized as a cancer chemopreventive agent. We aimed to investigate the anticancer effects of Apigenin in in-vivo studies to know its present research status and how close or how far it is from the clinics. Several electronic databases such as PubMed, Springer, Cochrane, and ctri.gov.in were searched to fetch the relevant articles. We focused only on published animal studies that reported the anticancer effects of Apigenin against various cancers. Two reviewers independently assessed the risk of bias for each analysis, and the conflicting views were resolved later by consensus. A total of 25 studies focused on the anticancer effects of Apigenin on various cancer types, including liver, prostate, pancreatic, lung, nasopharyngeal, skin, colon, colorectal, colitis-associated carcinoma, head and neck squamous cell carcinoma, leukemia, renal cell carcinoma, Ehrlich ascites carcinoma, and breast cancer were included. Overall, Apigenin reduces tumor volume (SMD=-3.597, 95% CI: -4.502 to -2.691, p < 0.001), tumor-weight (SMD=-2.213, 95% CI: -2.897 to -1.529, p < 0.001), tumor number (SMD=-1.081, 95% CI: -1.599 to -0.563, p < 0.001) and tumor load (SMD=-1.556, 95% CI: -2.336 to -0.776, p < 0.001). Further, it has no significant effect on the animal's body-weight (SMD=-0.345, 95% CI: -0.832 to 0.143, p = 0.165). Apigenin exerts anti-tumor effects mainly by inducing apoptosis/cell-cycle arrest. Our analysis suggests that Apigenin has potential anticancer effects against various cancers. However, the poor symmetry of the funnel plot suggested publication bias. Thus, it warrants further research to evaluate the potential of Apigenin alone or as an adjuvant for cancer treatment.