Foeniculum vulgare Mill.inhibits lipopolysaccharide-induced microglia activation and ameliorates neuroinflammation-mediated behavioral deficits in mice

Objective:To investigate the effect of Foeniculum vulgare extract against lipopolysaccharide(LPS)-induced microglial activation in vitro as well as cognitive behavioral deficits in mice.Methods:LPS-activated BV-2 cell viability was measured using MTT assay and reactive oxygen species(ROS)was studied using DCF-DA assay.The antioxidative enzymes and pro-inflammatory mediators were analyzed using respective ELISA kits and Western blotting.For in vivo testing,LPS(1 mg/kg,i.p.)was given daily for five days in male Swiss albino mice to produce chronic neuroinflammation.Cognitive and behavioral tests were performed using open-field,passive avoidance,and rotarod experiments in LPS-induced mice.Results:Foeniculum vulgare extract(25,50 and 100μg/mL)significantly attenuated the LPS-activated increase in nitric oxide(NO),ROS,cyclooxygenase-2,inducible NO synthase,IL-6,and TNF-alpha(P<0.05).Moreover,LPS-induced oxidative stress and reduced antioxidative enzyme levels were significantly improved by Foeniculum vulgare extract(P<0.05).The extract also regulated the NF-κB/MAPK signaling in BV-2 cells.In an in vivo study,Foeniculum vulgare extract(50,100,and 200 mg/kg)markedly mitigated the LPS-induced cognitive and locomotor impairments in mice.The fingerprinting analysis showed distinctive peaks with rutin,kaempferol-3-O-glucoside,and anethole as identifiable compounds.Conclusions:Foeniculum vulgare extract can ameliorate LPS-stimulated neuroinflammatory responses in BV-2 microglial cells and improve cognitive and locomotor performance in LPS-administered mice.

Protective effects of Foeniculum vulgare root bark extract against carbon tetrachloride-induced hepatic fibrosis in mice

AIM To investigate the protective effects of Foeniculum vulgare root bark (FVRB), a traditional Uyghur medicine, against carbon tetrachloride (CCl4)-induced hepatic fibrosis in mice. METHODS Mice were randomly divided into eight groups (n = 20 each). Except for the normal control group, mice in the rest groups were intraperitoneally injected (i.p.) with 0.1% CCl4-olive oil mixture at 10 mL/kg twice a week to induce liver fibrosis. After 4 wk, mice were treated concurrently with the 70% ethanol extract of FVRB (88, 176, 352 and 704 mg/kg, respectively) daily by oral gavage for 4 wk to evaluate its protective effects. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride (TG), hexadecenoic acid (HA), laminin (LN), glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) in liver tissues were measured. Hematoxylin-eosin (H and E) staining and Masson trichrome (MT) staining were performed to assess histopathological changes in the liver. The expression of transforming growth factor beta 1 (TGF-beta 1), matrix metalloprotein 9 (MMP-9) and metallopeptidase inhibitor 1 (TIMP-1) was detected by immunohistochemical analysis. Additionally, TGF-beta 1 and alpha-smooth muscle actin (alpha-SMA) protein expression was measured by Western blot. RESULTS A significant reduction in serum levels of AST, ALT, TG, HA and LN was observed in the FVRB-treated groups, suggesting that FVRB displayed hepatoprotective effects. Also, the depletion of GSH, SOD, and MDA accumulation in liver tissues was suppressed by FVRB. The expression of TGF-beta 1, MMP-9 and TIMP-1 determined by immunohistochemistry was markedly reduced in a dose-dependent manner by FVRB treatment. Furthermore, protective effects of FVRB against CCl4-induced liver injury were confirmed by histopathological studies. Protein expression of TGF-beta 1 and alpha-SMA detected by Western blot was decreased by FVRB treatment. CONCLUSION Our results indicate that FVRB may be a promising agent against hepatic fibrosis and its possible mechanisms are inhibiting lipid peroxidation and reducing collagen formation in liver tissue of liver fibrosis mice.

Comparative analysis of antioxidant activities of essential oils and extracts of fennel(Foeniculum vulgare Mill.)seeds from Egypt and China

The present study was conducted to assay the antioxidant activities of essential oils and ethanol extracts of fennel(Foeniculum vulgare Mill.)seeds from Egypt and China.The major components of the Egyptian fennel essential oil were estragole(51.04%),limonene(11.45%),l-fenchone(8.19%)and trans-anethole(3.62%)by GC–MS analysis.Whereas,the major constituents of Chinese fennel essential oil were transanethole(54.26%),estragole(20.25%),l-fenchone(7.36%)and limonene(2.41%).The fennel seed extracts from Egypt and China contained appreciable levels of total phenolic contents(42.24 and 30.94 mg PE/g,respectively).The extracts exhibited good DPPH radical scavenging capacity with IC50(6.34 and 7.17 mg/g),respectively.A high variation in free radical scavenging activities of essential oils was observed.The Chinese fennel essential oil showed high activity in DPPH radical scavenging with IC50(15.66 mg/g).The Egyptian fennel essential oil showed very low activity with IC50(141.82 mg/g).The results of the present investigation demonstrated significant variations in the antioxidant activities of fennel essential oils and extracts from Egypt and China.

Beneficial effects of Foeniculum vulgare on ethanol-induced acute gastric mucosal injury in rats

AIM： To examine the anti-ulcerogenic and antioxidant effects of aqueous extracts of Foeniculum vu/gare （FVE） on ethanol-induced gastric lesions in rats.METHODS： FVE was administered by gavage at doses of 75, i50 and 300 mg/kg, and famotidine was used at the dose of20mg/kg.Following a 60 min period, all the rats were given 1 mL of ethanol （80%） by gavage. One hour after the administration of ethanol, all groups were sacrificed, and the gastric ulcer index was calculated; whole blood malondialdehyde （MDA） and reduced glutathione （GSH）, serum nitrate, nitrite, ascorbic acid, retinol and β-carotene levels were measured in all the groups.RESULTS： It was found that pretreatment with FVE significantly reduced ethanol-induced gastric damage. This effect of FVE was highest and statistically significant in 300 mg/kg group compared with the control （4.18 ± 2.81 vs 13.15 ± 4.08, P 〈 0.001）. Also, pretreatment with FVE significantly reduced the MDA levels, while significantly increased GSH, nitrite, nitrate, ascorbic acid, retinol and β-carotene levels. CONCLUSION： FVE has clearly a protective effect against ethanol-induced gastric mucosal lesion, and this effect, at least in part, depends upon the reduction in lipid peroxidation and augmentation in the antioxidant activity.

Rescue effects of aqueous seed extracts of Foeniculum vulgare and Carum carvi against cadmium-induced hepatic, renal and gonadal damage in female albino rats

Objective: To investigate the protective effects of aqueous seed extracts of fennel"Foeniculum vulgare"(FVE) and caraway "Carum carvi"(CCE) on liver, kidney and reproductive organs in female rats against cadmium chloride(CC) intoxication.Methods: A total of 36 adult female rats were divided into six groups, six in each group.Control group(fed normal diet), CC-treated group(50 mg CC/kg diet), CCE-treated group(150 mg CCE/kg diet), CCE + CC group, FVE(150 mg/kg diet) and FVE + CC. One month later, all rats were sacrificed and all samples were collected at proestrus phase.Results: The toxic effects of CC were confirmed biochemically by significant increase of serum concentration of liver enzymes(P < 0.05), and creatinine(P < 0.001). Moreover,CC increased significantly the serum level of malondialdehyde(MDA) and decreased the total antioxidant capacity(TAC)(P < 0.001). In addition, serum concentrations of estrogen, progesterone, follicle-stimulating hormone(FSH) and luteinizing hormone(LH)were significantly decreased(P < 0.01). Histopathologically, CC-treated group revealed marked pathological changes in renal, hepatic, ovarian and uterine tissues. All toxic findings observed in liver and kidney with CC treatment were found to be ameliorated markedly after co-treatments with FVE or CCE. Furthermore, co-treatment of FVE with CC improved significantly all studied reproductive parameters(P < 0.01).Conclusions: Both FVE and CCE could be used as efficient treatments for liver and kidney against CC intoxication. Moreover, FVE could be utilized as a potent treatment to protect and improve female fertility from cadmium intoxication.

Efficacy of the herbal formula of Foeniculum vulgare and Rosa damascena on elderly patients with functional constipation:A double-blind randomized controlled trial

Background:Constipation is a common chronic bowel disorder with an incidence of more than 50%in the elderly population.Complementary and alternative medicine is a cost-effective and satisfactory treatment for constipation used widely by the elderly.Objective:This study evaluates the efficacy of an herbal formula made from Foeniculum vulgare Mill.and Rosa damascena for the treatment of constipation in an elderly population and consequent changes to their quality of life.Design,setting,participants and intervention:This double-blind randomized active controlled clinical trial,with parallel group allocation ratio of 1:1,was conducted in a referral clinic in Afzalipour Hospital,affiliated to Kerman University of Medical Sciences in Kerman,Southeastern Iran.Individuals over 60 years of age,diagnosed with functional constipation(based on the RomeⅣcriteria),were included in this study.Participants received a sachet of 10 g F.vulgare and R.damascena(herbal formula group)or polyethylene glycol 4000(PEG 4000 group)with a glass of warm water two times a day for 4 weeks and were followed up for 4 additional weeks.Main outcome measures:Constipation severity,stool consistency,and the quality of life were used as the primary outcomes.Drug side effects were used as a secondary outcome.The outcomes were assessed using the Constipation Assessment Scale,the Bristol Stool Form Scale,and the Patient Assessment of Constipation Quality of Life questionnaire.Results:A total of 25 participants in each group completed the four-week treatment cycle and the eightweek follow-up.At the end of the four-week treatment cycle,all clinical outcomes had significant improvements in both groups(P<0.05).The analysis of constipation severity(P<0.001),stool consistency(P<0.001),and the quality of life(P<0.001)showed significant improvements with fewer side effects(mild diarrhea)and a longer duration of symptom relief in the herbal formula group compared to the PEG 4000 group.Conclusion:Although both interventions significantly improved the treatment outcomes,constipation severity,stool consistency and the quality of life were improved more effectively by the herbal formula than by PEG 4000;however,the mechanism of action is not yet understood.Trial registration:This trial was registered in the Iranian Registry of Clinical Trials(IRCTID:IRCT20200108046056N1).

Medicinal Properties of Foeniculum Vulgare Mill,in Traditional Iranian Medicine and Modern Phytotherapy

Foeniculum vu/gare Mill. （F. vu/gare）, commonly known as Fennel, is a popular medicinal plant with various pharmacological activities mentioned in traditional Iranian medicine （TIM） and modern phytotherapy such as antioxidant, cytotoxic, anti-inflammatory, antimicrobial, bronchodilatory, estrogenic, diuretic, lithontripic, galactogogue, emmenagogue, antithrombotic, hypotensive, gastroprotective, hepatoprotective, memory enhancing, and antimutagenic activities. No serious adverse events were recorded after ingestion of F. vu/gare except some cases of allergic reactions. The estrogenic activity of F. vu/gare brings some side effects such as decrease in protein concentration and acid and alkaline phosphatase in male genital organs, increase in weight of mammary glands and reproductive organs in women and premature thelarohe in girls. However, no evidence of teratogenicity was recorded, it is better not to use F. vulgare during pregnancy due to its estrogenic activity. Because of inhibition of cytochrome P450 3A4 （CYP3A4）, the pharmacokinetic parameters of drugs mainly metabolized by this isozyme may be affected by F. vu/gare. In addition, a significant interaction between cyprofloxacin and F. vu/gare was demonstrated. The aim of current paper is to review pharmacological properties, toxicity and adverse events, and drug interactions of F.vu/gare and brings conclusive results about the use of this plant in men, women and during pregnancy.