Optimization of Aqueous Extraction of Polyphenols from Cuminum cyminum Seeds Using Response Surface Methodology and Assessment of Biological Activity.

(1) Background: Cumin seeds, extracted from the plant Cuminum cyminum, are abundant in phenolic compounds and have been extensively researched for their chemical makeup and biological effects. The objective of this research is to enhance the water extraction of polyphenols through the water bath (WB) technique and to evaluate the antiradical, antibacterial, and anticancer effects of the extract. (2) Methods: Response Surface Methodology was used to find the best parameters to extract polyphenols. Three experimental parameters, time, temperature, and solid-liquid ratio, were tested. The disc diffusion method has been used to determine the antimicrobial activities against Salmonella Typhimurium, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, and Candida albicans. The antiradical activity was performed using the DPPH method, while total phenolic content was performed using Folin-Ciocalteu. High-Performance Liquid Chromatography (HPLC) was conducted to analyze the phytochemical profile of WB extracts. The anticancer activity of the lyophilized extract was assessed against three cancer cell lines (colon (HT29), lung (A549), and breast (MCF7) cancer cell lines).; (3) Results: The optimal conditions for water extraction were 130 min at 72 °C. The total phenolic compounds yield (14.7 mg GAE/g DM) and antioxidant activity (0.52 mg trolox eq./mL) were obtained using a 1:40 solid-liquid ratio. The primary polyphenols identified were the flavonoids rutin (0.1 ppm) and ellagic acid (3.78 ppm). The extract had no antibacterial or antifungal activities against the microorganisms tested. The extract showed anticancer activity of about 98% against MCF7 (breast cancer cell line), about 81% against HT29 (colon cancer cell line), and 85% against A549 (lung cancer cell line) at high doses. (4) Conclusions: Extraction time and a high solid-liquid ratio had a positive impact on polyphenol recovery and in maintaining their quantity and quality. Furthermore, the optimal aqueous extract exhibited strong antiradical activity reflected by the inhibition of free radicals in addition to a significant specificity against the tested cancer cell lines.

Increasing the efficiency of cumin essential oil extraction using cold plasma pretreatments.

BACKGROUND: Cumin (Cuminum cyminum L.) is one of the most important medicinal plants, and its essential oil (EO) varies between 2.5% to 5% depending on differences in climate. The extraction method plays a significant role in the market price of EOs. In this study, the effect of atmospheric cold plasma (ACP) pretreatments (using air and argon (Ar) gases) for different times on the EO yield and on the quality, color, surface morphology, and wettability of cumin seeds were studied. RESULTS: The scanning electron microscope analysis results revealed that the formation of fissures and cracks caused by ACP pretreatments was directly related to increasing the efficiency of EO extraction. Comparing the two gas treatments, the highest total color changes ΔE were related to the Ar and the lowest to the air treatment, and the highest amount of browning index was related to the Ar ACP pretreatment. In general, the ACP pretreatments improved the extraction efficiency compared with the control, so that the highest increase was observed in the Ar ACP pretreatment at the rate of 44%. Ar ACP pretreatments were observed to have a higher extraction efficiency than air ACP did. In the Ar ACP-treated samples, cumin aldehyde, as the most important component of EO, was increased compared with the control (47.9-56.4%). CONCLUSION: The data obtained in this study showed that ACP pretreatment of cumin seeds could increase EO extraction efficacy. Thus, ACP could be a promising technique to enhance the cumin seed EO extraction. © 2024 Society of Chemical Industry.

Resistant cumin cultivar, GC-4 counters Fusarium oxysporum f. sp. cumini infection through up-regulation of steroid biosynthesis, limonene and pinene degradation and butanoate metabolism pathways.

Cumin (Cuminum cyminum L.), an important spice crop belonging to the Apiaceae family is infected by Fusarium oxysporum f. sp. cumini (Foc) to cause wilt disease, one of the most devastating diseases of cumin adversely affects its production. As immune responses of cumin plants against the infection of Foc are not well studied, this research aimed to identify the genes and pathways involved in responses of cumin (cv. GC-2, GC-3, GC-4, and GC-5) to the wilt pathogen. Differential gene expression analysis revealed a total of 2048, 1576, 1987, and 1174 differentially expressed genes (DEGs) in GC-2, GC-3, GC-4, and GC-5, respectively. In the resistant cultivar GC-4 (resistant against Foc), several important transcripts were identified. These included receptors, transcription factors, reactive oxygen species (ROS) generating and scavenging enzymes, non-enzymatic compounds, calcium ion (Ca2+) transporters and receptors, R-proteins, and PR-proteins. The expression of these genes is believed to play crucial roles in conferring resistance against Foc. Gene ontology (GO) analysis of the up-regulated DEGs showed significant enrichment of 19, 91, 227, and 55 biological processes in GC-2, GC-3, GC-4, and GC-5, respectively. Notably, the resistant cultivar GC-4 exhibited enrichment in key GO terms such as 'secondary metabolic process', 'response to reactive oxygen species', 'phenylpropanoid metabolic process', and 'hormone-mediated signaling pathway'. Furthermore, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed the enrichment of 28, 57, 65, and 30 pathways in GC-2, GC-3, GC-4, and GC-5, respectively, focusing on the up-regulated DEGs. The cultivar GC-4 showed enrichment in pathways related to steroid biosynthesis, starch and sucrose metabolism, fatty acid biosynthesis, butanoate metabolism, limonene and pinene degradation, and carotenoid biosynthesis. The activation or up-regulation of various genes and pathways associated with stress resistance demonstrated that the resistant cultivar GC-4 displayed enhanced defense mechanisms against Foc. These findings provide valuable insights into the defense responses of cumin that could contribute to the development of cumin cultivars with improved resistance against Foc.

Cuminum cyminum Ameliorates Urotoxic Effects of Cyclophosphamide by Modulating Antioxidant, Inflammatory Cytokines, and Urinary Bladder Overactivity: In vivo and in Silico Investigations.

Interstitial Cystitis (IC) is a chronic inflammatory disease that lacks effective treatment. The present study aimed to investigate the potential of aqueous ethanol extract of Cuminum cyminum (AEECC) on oxidative stress, inflammation and overactivity of urinary bladder induced by cyclophosphamide (CYP). Female Sprague-Dawley rats received intraperitoneal administration of cyclophosphamide (150 mg/kg, i. p. 1st , 4th , and 7th days). To investigate the urothelial damage, the bladder weight, nociception behavior, and Evans blue dye extravasation method was used. The antioxidants CAT, GPX and NO were measured. ELISA determined the IL-6 and TNF-α levels. The spasmolytic effect of AEECC was investigated on isolated bladder strips and its mechanisms were determined. The enhanced nociception behavior, bladder weight, vascular permeability, edema, hemorrhage, nitric oxide, IL-6 and TNF-α levels by CYP administration were significantly reduced by AEECC (250 and 500 mg/kg). A significant increase in serum antioxidant system such as CAT and GPx was also observed in AEECC-treated rats. The AEECC (3 mg/ml) significantly reduced urinary bladder tone in the strips pre-contracted with carbachol in both control and CYP-treated rats. This relaxation was demolished by atropine, nifedipine, glibenclamide, and indomethacin but not with propranolol. The plant extract showed the presence of antioxidant and anti-inflammatory phytochemicals. These results suggest that Cuminum cyminum offers uroprotective activity and can ameliorate CYP-induced bladder toxicity by modulating antioxidant parameters, pro-inflammatory cytokine levels and bladder smooth muscle overactivity. The in silico binding interactions of antioxidant 2I3Y and anti-inflammatory protein 1TNF with various ligands from Cuminum cyminum seeds revealed potential bioactive compounds with promising antioxidant and anti-inflammatory properties, providing valuable insights for drug development and nutraceutical research.

Effects of Cuminum cyminum L. essential oil and its nanoemulsion on oxidative stability and microbial growth in mayonnaise during storage.

The present study aimed to investigate the effects of Cuminum cyminum L. essential oil (CEO) and its nanoemulsion (CEON) on oxidative stability and microbial growth of mayonnaise during storage. The GC analysis indicated that Cuminaldehyde (27.99%), o-Cymene (17.31%), γ-Terpinen (16.67%), and ß-Pinene (9.35%) were the major components of CEO, respectively. The assessments of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) showed that Escherichia coli ATCC 25922 (MBCCEO = 12 and MBCCEON = 6 mg/mL) was the most resistant bacteria, and in contrast, Staphylococcus aureus ATCC 29213 (MBCCEO = 6 and MBCCEON = 3 mg/mL) was the most sensitive bacteria. In the radical-scavenging assay, CEON (IC50 = 5 ± 0.07 µg/mL) exhibited a higher antioxidant activity than CEO (IC50 = 10 ± 0.13 µg/mL). The results showed that applying the MBC of CEO and CEON in mayonnaise led to a significant decrease (p < .05) in acidity, peroxide value, number of acid-resistant bacteria and fungi, and total microbial count compared with the control sample. In conclusion, this study demonstrated that using CEON resulted in oxidative stability, microbial growth control, and desirable sensorial attributes in mayonnaise compared with CEO and control samples.

Activity of cumin essential oil to control fascioliasis: Efficacy and changes in the tegument of Fasciola hepatica.

Fasciola hepatica, the liver trematode, infects ruminants and causes economic loss. Because parasites are developing resistance to commercial drugs, the negative effects of parasitism are increasing. In this study, we aimed to evaluate the efficacy of cumin (Cuminum cyminum) essential oil against F. hepatica eggs and adults. The eggs were incubated with eight concentrations of the essential oil (0.031125-4.15 mg/mL), and viable eggs were counted after 14 days and classified as embryonated or non-embryonated. Adult flukes were incubated in Roswell Park Memorial Institute medium to ensure their viability and then incubated in essential oil. They were observed for 24 h after treatment. The adults were assessed with the two lowest effective oil concentrations used in the ovicidal test. Three controls were used for both tests: nitroxynil, a negative control, and Tween®80. After incubation in oil, the adult specimens were processed for histological analysis and stained with hematoxylin-eosin. In addition, the oil was tested for cytotoxicity using Madin-Darby bovine kidney cells to assess any possible effect on them. The oil was effective in ovicidal and adulticidal inhibition of the trematode, with statistically significant results. All concentrations assessed in the ovicidal test were 100% effective. The adult test was effective within 15 h and inactivated all the specimens at the highest concentration evaluated (0.06225 mg/mL). Histological analysis showed that cumin essential oil resulted in marked areas of vacuolization. The spines showed no structural changes but were surrounded by microvesicles. These findings indicated that cumin oil could be a potential compound in the control of fasciolosis.

The complete mitochondrial genome of Cuminum cyminum (Apiales: Apiaceae) and phylogenetic analysis.

Cumin (Cuminum cyminum L). belongs to the family Apiaceae and the order Apiales, which is a widely grown spice and medicinal plant in Xinjiang province, China. In the current study, whole genome sequencing of C. cyminum was performed using the Illumina HiSeq 4000 platform, and the complete mitogenome sequence was assembled and annotated. We found that the single circular mitogenome of C. cyminum was 246,721 bp in length, and has about 45.5% GC content. It comprised 73 genes in the coding region (35 protein-coding genes, 18 tRNA genes, 3 rRNA genes, and 15 open-reading frames) and a non-coding region. Phylogenetic analysis indicated that C. cyminum is closely related to Daucus carota and the subtribes Daucinae. The mitogenome of C. cyminum revealed its phylogenetic relationships with other species in the Apiaceae family, which would further help in understanding its evolution.

Identification of Cumin (Cuminum cyminum) MicroRNAs through Deep Sequencing and Their Impact on Plant Secondary Metabolism.

The pharmacological properties of plants lie in the content of secondary metabolites that are classified into different categories based on their biosynthesis, structures, and functions. MicroRNAs (miRNAs) are small non-coding RNA molecules that play crucial post-transcriptional regulatory roles in plants, including development and stress-response signaling; however, information about their involvement in secondary metabolism is still limited. Cumin is one of the most popular seeds from the plant Cuminum cyminum, with extensive applications in herbal medicine and cooking; nevertheless, no previous studies focus on the miRNA profile of cumin. In this study, the miRNA profile of C. cyminum and its association with the biosynthesis of secondary metabolites were determined using NGS technology. The sequencing data yielded 10,956,054 distinct reads with lengths ranging from 16 to 40 nt, of which 349 miRNAs were found to be conserved and 39 to be novel miRNAs. Moreover, this work identified 1959 potential target genes for C. cyminum miRNAs. It is interesting to note that several conserved and novel miRNAs have been found to specifically target important terpenoid backbone, flavonoid biosynthesis, and lipid/fatty acid pathways enzymes. We believe this investigation will aid in elucidating the implications of miRNAs in plant secondary metabolism.

Natural sanitizer potential of Cuminum cyminum and applicable approach for calculation of Kováts retention index of its compounds.

The demand for natural agents instead of chemicals in terms of food and health safety is increasing day by day. This study aimed to investigate the potential of the methanolic extract of Cuminum cyminum (C. cyminum) in the fight against Escherichia coli (E. coli), Staphylococcus aureus (S. aureus)and Candida (C. albicans). The chemical composition of the methanolic extract of C. cyminum was analyzed using GS-MS. Also, Kováts retention indices were calculated for the detected compounds using an applicable formula. The most basic substance was cuminic aldehyde (27.86%) and p-(Dimethoxymethyl)-isopropylbenze (18.32%). The Minimum Inhibitory Concentration (MIC) of the extract was 0.1 g/mL for S. aureus and C. albicans while it was > 0.1 for E. coli. Although the methanol extract of C. cyminum acts against all three microorganisms, the most lasting effect was on S. aureus, indicating that it can be recommended as a strong antibacterial disinfectant for S. aureus.

Phytochemical screening of ethanolic extracts of Cuminum cyminum L. seeds along with the evaluation of antidiabetic properties by molecular docking approach.

In this contribution, ethanolic extracts of Cuminum cyminum (C. cyminum) seeds were evaluated in terms of phytochemical content, total phenol and flavonoid contents. As far as the analytical techniques are concerned, UV-Vis, FTIR, HPLC, NMR (1H and 13C) and ESI-MS were performed. The binding capacity of five different antidiabetic enzymes was tested by in silico molecular docking studies. The HPLC, UV-Vis, FTIR, NMR and ESI-MS data highlighted the presence of seven biologically active molecules e.g. α-pinene, ß-pinene, Δ3-carene, ρ-cymene, α-terpineol, cuminaldehyde and linalool. The results coming from the in silico molecular docking studies showed that such phytochemicals present in the cumin seed extracts play an important role in the activity of key enzymes involved in carbohydrate metabolism. Therefore, C. cyminum is proven to be useful for the treatment of diabetes mellitus and its major secondary complications.

Effective adsorption of diclofenac sodium from aqueous solution using cationic surfactant modified Cuminum cyminum agri-waste: kinetic, equilibrium, and thermodynamic studies.

The occurrence of pharmaceutical pollutants in aqueous media has increased where significant research is being conducted to eliminate these toxic compounds. In the present study, Tetradecyltrimethylammonium bromide (TTAB) modified Cuminum cyminum agri-waste (CCW) was prepared to investigate the removal of diclofenac sodium (DCF) from aqueous solution in the batch process for the first time. Physical and chemical characterizations of as-prepared adsorbent were conducted using field emission scanning electron microscopy, Fourier-transform infrared spectroscopy, N2 adsorption-desorption, and point of zero charge analysis. Besides, the effect of the main parameters that affect the adsorption process, i.e., adsorbent dosage (0.25-6 g/L), contact time (0-300 min), initial DCF concentration (10-500 mg/L), and pH of the solution, were investigated. Furthermore, the resulted data were analyzed using various kinetic and isotherm models. The Pseudo-second-order model with R2 = 0.9981 showed the highest agreement with kinetic behavior. Also, the maximum adsorption capacity of DCF is 93.65 mg/g, according to the Langmuir isotherm. In acidic media, the adsorption capacity reached the highest value (44.69 mg/g). As a result, this study revealed that the agri-waste material could be modified and, as a low-cost adsorbent, have promising adsorption potential to remove pharmaceutical contaminants from the aqueous solution.

In this study, an innovative agricultural waste, Cuminum cyminum, has been used as low-cost material and modified with Tetradecyltrimethylammonium bromide cationic surfactant to remove diclofenac sodium (DCF) from aqueous solution in the batch process for the first time. TTAB-modified CCW exhibited an excellent adsorption capacity of 93.65 mg/g. Kinetic and equilibrium investigations were conducted with various models in detail.

Safety and efficacy of a feed additive consisting of an essential oil from the fruit of Cuminum cyminum L. (cumin oil) for use in all animal species (FEFANA asbl).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of an essential oil obtained from the fruit of Cuminum cyminum L. (cumin oil), when used as a sensory additive in feed and water for drinking for all animal species. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the use of cumin oil up to the maximum proposed use levels in feed of 15 mg/kg complete feed is considered as safe for all animal species. The FEEDAP Panel considered the use in water for drinking as safe provided that the total daily intake of the additive does not exceed the daily amount that is considered safe when consumed via feed. No concerns for consumers were identified following the use of cumin oil up to the maximum proposed use level in feed. The additive under assessment should be considered as irritant to skin and eyes, and as a dermal and respiratory sensitiser. When handling the essential oil, exposure of unprotected users to estragole (and dillapiole) cannot be excluded. Therefore, to reduce the risk, the exposure of the users should be minimised. The use of cumin oil at the proposed use level in feed is not expected to pose a risk to the environment. Since C. cyminum and its preparations are recognised to flavour food and its function in feed would be essentially the same as that in food, no further demonstration of efficacy is considered necessary.

GC-MS Profiling, Anti-Helicobacter pylori, and Anti-Inflammatory Activities of Three Apiaceous Fruits' Essential Oils.

Eradication of Helicobacter pylori is a challenge due to rising antibiotic resistance and GIT-related disorders. Cuminum cyminum, Pimpinella anisum, and Carum carvi are fruits belonging to the Apiaceae family. Their essential oils were extracted, analyzed using GC-MS, tested for anti-H. pylori activity by a micro-well dilution technique, identified for potential anti-H. pylori inhibitors by an in-silico study, and investigated for anti-inflammatory activity using a COX-2 inhibition assay. Results showed that the main components of C. cyminum, P. anisum, and C. carvi were cumaldehyde (41.26%), anethole (92.41%), and carvone (51.38%), respectively. Essential oil of C. cyminum exhibited the greatest anti-H. pylori activity (3.9 µg/mL) followed by P. anisum (15.63 µg/mL), while C. carvi showed the lowest activity (62.5 µg/mL). The in-silico study showed that cumaldehyde in C. cyminum has the best fitting energy to inhibit H. pylori.C. cyminum essential oil showed the maximum ability to reduce the production of Cox-2 expression approaching celecoxib with IC50 = 1.8 ± 0.41 µg/mL, followed by the C. carvi oil IC50 = 7.3 ± 0.35 µg/mL and then oil of P. anisum IC50 = 10.7±0.63 µg/mL. The investigated phytochemicals in this study can be used as potential adjunct therapies with conventional antibiotics against H. pylori.

In Vitro and In Silico Screening of Anti-Vibrio spp., Antibiofilm, Antioxidant and Anti-Quorum Sensing Activities of Cuminum cyminum L. Volatile Oil.

Cuminum cyminum L. essential oil (cumin EO) was studied for its chemical composition, antioxidant and vibriocidal activities. Inhibition of biofilm formation and secretion of some virulence properties controlled by the quorum sensing system in Chromobacterium violaceum and Pseudomonas aeruginosa strains were also reported. The obtained results showed that cuminaldehyde (44.2%) was the dominant compound followed by ß-pinene (15.1%), γ-terpinene (14.4%), and p-cymene (14.2%). Using the disc diffusion assay, cumin EO (10 mg/disc) was particularly active against all fifteen Vibrio species, and the highest diameter of growth inhibition zone was recorded against Vibrio fluvialis (41.33 ± 1.15 mm), Vibrio parahaemolyticus (39.67 ± 0.58 mm), and Vibrio natrigens (36.67 ± 0.58 mm). At low concentration (MICs value from 0.023-0.046 mg/mL), cumin EO inhibited the growth of all Vibrio strains, and concentrations as low as 1.5 mg/mL were necessary to kill them (MBCs values from 1.5-12 mg/mL). Using four antioxidant assays, cumin EO exhibited a good result as compared to standard molecules (DPPH = 8 ± 0.54 mg/mL; reducing power = 3.5 ± 0.38 mg/mL; ß-carotene = 3.8 ± 0.34 mg/mL; chelating power = 8.4 ± 0.14 mg/mL). More interestingly, at 2x MIC value, cumin EO inhibited the formation of biofilm by Vibrio alginolyticus (9.96 ± 1%), V. parahaemolyticus (15.45 ± 0.7%), Vibrio cholerae (14.9 ± 0.4%), and Vibrio vulnificus (18.14 ± 0.3%). In addition, cumin EO and cuminaldehyde inhibited the production of violacein on Lauria Bertani medium (19 mm and 35 mm, respectively). Meanwhile, 50% of violacein inhibition concentration (VIC50%) was about 2.746 mg/mL for cumin EO and 1.676 mg/mL for cuminaldehyde. Moreover, elastase and protease production and flagellar motility in P. aeruginosa were inhibited at low concentrations of cumin EO and cuminaldehyde. The adopted in-silico approach revealed good ADMET properties as well as a high binding score of the main compounds with target proteins (1JIJ, 2UV0, 1HD2, and 3QP1). Overall, the obtained results highlighted the effectiveness of cumin EO to prevent spoilage with Vibrio species and to interfere with the quorum sensing system in Gram-negative bacteria by inhibiting the flagellar motility, formation of biofilm, and the secretion of some virulence enzymes.

Natural essential oil mix of sweet orange peel, cumin, and allspice elicits anti-inflammatory activity and pharmacological safety similar to non-steroidal anti-inflammatory drugs.

An inflammation response occurs when the body reacts to exogenous and endo enous noxious stimuli, and it helps the body respond to infection and repair tissues, adapt to stress, and remove dead or damaged cells. Anti-inflammatory drugs such as non-steroidal anti-inflammatory drugs are traditionally used to treat inflammation; however, these drugs often cause negative side effects. For this reason, developing and establishing effective alternative medicines for treating many chronic diseases with underlying inflammation is critically dependent on the identification of new organic molecules and bioactive substances. Aromatic and volatile compounds found in essential oils isolated from Pimenta dioica (allspice), Cuminum cyminum (cumin), and Citrus sinensis (sweet orange) are a source of bioactive compounds. Allspice essential oil reduces ear inflammation more than 65% and the anti-inflammatory activity of allspice essential oil is enhanced when combined with sweet orange peel and cumin essential oils, resulting in the reduction of edema inflammation by more than 85%, similar to indomethacin. As an alternative to anti-inflammatory treatment, essential oil mix is pharmacologically safe as it is neither toxic nor mutagenic.

Umbelliferose Isolated from Cuminum cyminum L. Seeds Inhibits Antigen-Induced Degranulation in Rat Basophilic Leukemia RBL-2H3 Cells.

Cuminum cyminum L. (cumin) is an annual plant of the Umbelliferae family native to Egypt. We previously showed that the aqueous extract of cumin seeds suppresses degranulation by downregulating the activation of antigen-induced intracellular signaling molecules in rat basophilic leukemia RBL-2H3 cells. However, the active substances in the extract have not yet been identified. Accordingly, herein, we aimed to ascertain the water-soluble substances present in cumin seeds that inhibit degranulation, which led to the identification of umbelliferose, a characteristic trisaccharide present in plants of the Umbelliferae family. Our study is the first to reveal the degranulation-suppressing activity of umbelliferose, and quantification studies suggest that cumin seed powder contains 1.6% umbelliferose. Raffinose, an isomer of umbelliferose, was also found to significantly suppress antigen-induced degranulation, but less so than umbelliferose. Both umbelliferose and raffinose contain sucrose subunits in their structures, with galactose moieties bound at different sites. These differences in structure suggest that the binding of galactose to the sucrose subunit at the α1-2 bond contributes to its strong degranulation-inhibiting properties.

Effect of C. cyminum and L. sativum on Pharmacokinetics and Pharmacodynamics of Antidiabetic Drug Gliclazide.

BACKGROUND: Numerous herbs are reported to have anti-hyperglycemic activity and are frequently used in combination with prescription drugs to lower the blood glucose levels in diabetic patients, without proper knowledge about the possibility of herb-drug interaction. OBJECTIVES: To investigate the effect of cumin and garden cress on pharmacokinetics (PK) and pharmacodynamics (PD) of gliclazide (GLZ) in nicotinamide-streptozotocin diabetic model. METHODS: Diabetic animals of groups II-IV were treated with GLZ, cumin, 'cumin + GLZ', garden cress and 'garden cress + GLZ'. Herb's treatments were given for two weeks, and GLZ was administered in a single dose. Blood glucose levels (BGLs) were measured at pre-determined time points. Plasma samples of pharmacokinetic study were analyzed using UPLC-MS/MS. GLZ fragment at m/z 324.1>127 was monitored. RESULTS: Cumin and garden cress have shown 15.3% and 15.9% reduction in mean BGL (1-24h) (p-value < 0.001), respectively. GLZ reduced mean BGL by 30.0%, which was significantly better than cumin and garden cress (pvalue <0.05). Concurrently administered "garden cress + GLZ" demonstrated the highest reduction in mean BGL (by 40.46%) and showed a prolonged effect. There was no significant advantage of simultaneously administered 'cumin + GLZ'. Cumin did not affect PK of GLZ. Garden cress has significantly enhanced AUC0-t (by 69.8%, pvalue 0.0013), but other PK parameters Cmax, Tmax, and Kel were close to the control group. CONCLUSION: PK/PD-based herb-drug interaction was observed. Concurrently administered garden cress + GLZ showed improved antidiabetic effect and has enhanced GLZ bioavailability.

A Green Approach for the Biosynthesis of Gold Nanoparticles Using Cuminum cyminum L. Seed and Its Application for Pain Management in Rats.

Background: This study investigated the antinociceptive effect of cumin and its biosynthesized gold nanoparticles (AuNPs). Methods: Cumin extract (E) and cumin-AuNPs (GN) were prepared and administered intraperitoneally at the concentrations of 200, 500, and 1000 mg/ml to 27 male rats. Ultraviolet-visible spectroscopy and atomic force microscopy were applied for AuNPs synthesis confirmation. The nociceptive behavior was assessed, and IL-6 serum levels were measured. Results: Cumin-AuNPs showed a peak absorption of 515 nm, and a size of about 40 nm. Three different concentrations of extract had no significant effect on acute and chronic nociceptive behavior. GN + E200 (46.00 ± 10.59) showed a significant acute anti-nociceptive effect compared to the control (98.66 ± 4.91; p = 0.029) and SS300 (98.33 ± 20.30; p = 0.029) groups. Also, GN + E500 (42.00 ± 11.84) significantly reduced acute nociceptive behavior compared to the control (98.66 ± 4.91; p = 0.019), SS300 (98.33 ± 20.30; p = 0.020), and GN + E1000 (91.00 ± 26.00; p = 0.040) groups. IL-6 serum levels reduced significantly in GN + E500 (24.65 ± 10.38; p = 0.002) and SS300 (33.08 ± 1.68; p = 0.039) compared to the controls (46.24 ± 3.02). Chronic nociceptive behavior was significantly lower in the SS300 (255.33 ± 26.30) compared to E200 (477.00 ± 47.29; p = 0.021), E500 (496.25 ± 46.29; p = 0.013), and GN + E500 (437.00 ± 118.03; p = 0.032) groups. Conclusion: Our findings suggest the potential effects of cumin-AuNPs on formalin-induced nociceptive behavior, which is independent of IL-6serum levels.

Aqueous Extract from Cuminum cyminum L. Seed Alleviates Ovalbumin-Induced Allergic Rhinitis in Mouse via Balancing of Helper T Cells.

Cuminum cyminum L. (cumin) seeds are widely used as a spice. Although we previously reported that the aqueous extract of cumin seeds suppresses the degranulation of rat basophilic RBL-2H3 cells, it has not been clarified whether the extract alleviates actual allergy symptoms in vivo. Therefore, in this study, we investigated the effect of oral administration of cumin seed aqueous extract (CAE) in ovalbumin (OVA)-induced allergic rhinitis. BALB/c mice were randomly divided into the following three groups: control group (five mice), OVA group (five mice), and OVA + CAE group (five mice). Allergic rhinitis was induced by sensitization (intraperitoneal, 25 µg OVA and 1.98 mg aluminum hydroxide gel) followed by challenge (intranasal, 400 µg OVA). The oral administration of CAE (25 mg/kg) reduced the sneezing frequency of OVA-induced allergic rhinitis model mice. In addition to reducing the serum immunoglobulin E and IL-4 levels, the oral administration of CAE reduced the production of T-helper type-2 (Th2) cytokines (IL-4, IL-5, IL-10, and IL-13) in the splenocytes of the model mice. Furthermore, a significant increase in the ratio of Th1 to Th2 cells was observed in the CAE-administered group. Our findings suggest that the ingestion of CAE improves T cell balance, the dominant state of Th2, and alleviates allergic rhinitis symptoms.

Development of a novel nanoemulgel formulation containing cumin essential oil as skin permeation enhancer.

Essential oils have been proposed as promising non-toxic transdermal permeation enhancers. Their use is limited because of their low water solubility. The use of nanotechnology-based strategies is one of the ways to overcome this limitation. This study aimed to explore the transdermal permeation enhancing capability of cumin essential oil in nanoemulgel systems containing diclofenac sodium. Cumin essential oil nanoemulsion was produced by high-pressure homogenization technique. The formulation was optimized by changing HLB values in a range of 9.65-16.7 using different surfactant mixtures, namely, Tween 20, Tween 80, and Span 80. Preparations were characterized by polydispersity index, droplet size, and zeta potential. Nanoemulsion with concentrations of 2 and 4% essential oil was incorporated into 0.75% Carbopol gel matrix to make nanoemulgel formulation, and its permeation enhancing effect was performed through Franz diffusion cells. Antinociceptive activities of the formulations were measured in thermal (tail-flick) and chemical (formalin) models of nociception in mice. Characterization exhibited that at HLB value of 9.65, the smallest particle size (82.20 ± 5.82 nm) was formed. By increasing the essential oil percentage in the nanoemulgel from 1 to 2%, the permeation of diclofenac increased from 28.39 ± 1.23 to 34.75 ± 1.07 µg/cm2 at 24 h. The value of permeation from the simple gel (21.18 ± 2.51 µg/cm2) and the marketed product (22.97 ± 1.92 µg/cm2) was lower than the formulations containing essential oil. Nanoemulgel of diclofenac containing essential oil showed stronger antinociceptive effects in formalin and tail-flick tests than simple diclofenac gel and marketed formulation. In conclusion, the study proved that nanoemulgel formulation containing cumin essential oil could be considered as a promising skin enhancer to enhance the therapeutic effect of drugs.