Exploring the multifaceted effects of Ammi visnaga: subchronic toxicity, antioxidant capacity, immunomodulatory, and anti-inflammatory activities.

Ammi visnaga (A. visnaga) is an annual herb that has been used in traditional medicine to treat various ailments attributed to the presence of its bioactive compounds. The purpose of this study was to identify and examine the phytochemical properties of the hydroalcoholic extract of A. visnaga using in vitro and in vivo models. Our findings demonstrated that the extract contained a variety of beneficial components, including phenols, flavonoids, tannins, coumarins, saponins, khellin, and visnagin. The total polyphenolic content and total flavonoid content were 23.26 mg/GAE/g dry weight and 13.26 mg/GAE/g dry weight, respectively. In vitro tests demonstrated that the extract possessed antioxidant properties as evidenced by the ability to scavenge free radicals, including DPPH, ABTS, nitric oxide (NO), phosphomolybdate, and ferric-reducing antioxidant power (FRAP). Further, the extract was found to inhibit hydrogen peroxide (H2O2)-induced hemolysis. In a 90-d in vivo study, female Wistar rats were administered 1 g/kg of A. visnaga extract orally resulting in a significant increase in total white blood cell count. Although morphological changes were observed in the liver, no marked alterations were noted in kidneys and spleen. In a female Swiss albino mice model of acetic acid-induced vascular permeability, A. visnaga significantly inhibited extravasations of Evans blue at doses of 0.5 or 1 g/kg with inhibition percentages of 51 and 65%, respectively, blocking tissue necrosis. The extract also demonstrated potential immunomodulatory properties in mice by enhancing antibody production in response to antigens. In silico molecular docking studies demonstrated a strong affinity between khellin or visnagin and immunomodulatory proteins, NF-κB, p52, and TNF-α. These findings suggest that A. visnaga may be considered a beneficial antioxidant with immunomodulatory properties and might serve as a therapeutic agent to combat certain diseases.

Quantitative Analysis of Isopimpinellin from Ammi majus L. Fruits and Evaluation of Its Biological Effect on Selected Human Tumor Cells.

Ammi majus L. (Apiaceae) is a medicinal plant with a well-documented history in phytotherapy. The aim of the present work was to isolate isopimpinellin (5,8-methoxypsoralen; IsoP) from the fruit of this plant and evaluate its biological activity against selected tumor cell lines. The methanol extract obtained with the use of an accelerated solvent extraction (ASE) method was the most suitable for the quantitative analysis of coumarins in the A. majus fruit matrix. The coumarin content was estimated by RP-HPLC/DAD, and the amount of IsoP was found to be 404.14 mg/100 g dry wt., constituting 24.56% of the total coumarin fraction (1.65 g/100 g). This, along with the presence of xanthotoxin (368.04 mg/100 g, 22.36%) and bergapten (253.05 mg/100 g, 15.38%), confirmed A. majus fruits as an excellent source of these compounds. IsoP was isolated (99.8% purity) by combined liquid chromatography/centrifugal partition chromatography (LC/CPC) and tested for the first time on its antiproliferative activity against human colorectal adenocarcinoma (HT29, SW620), osteosarcoma (Saos-2, HOS), and multiple myeloma (RPMI8226, U266) cell lines. MTT assay results (96 h incubation) demonstrated a dose- and cell line-dependent decrease in cell proliferation/viability, with the strongest effect of IsoP against the Saos-2 cell line (IC50; 42.59 µM), medium effect against U266, HT-29, and RPMI8226 (IC50 = 84.14, 95.53, and 105.0 µM, respectively), and very weak activity against invasive HOS (IC50; 321.6 µM) and SW620 (IC50; 711.30 µM) cells, as well as normal human skin fibroblasts (HSFs), with IC50; 410.7 µM. The mechanistic study on the Saos-2 cell line showed that IsoP was able to reduce DNA synthesis and trigger apoptosis via caspase-3 activation. In general, IsoP was found to have more potency towards cancerous cells (except for HOS and SW620) than against healthy cells. The Selective Index (SI) was determined, underlining the higher selectivity of IsoP towards cancer cells compared to healthy cells (SI = 9.62 against Saos-2). All these results suggest that IsoP might be a promising molecule in the chemo-prevention and treatment of primary osteosarcoma.

Molecular Docking and Dynamics Simulations of Ammi visnaga L. Constituents as Antimelanogenic, Anti-Inflammatory and Anticoagulant Agents.

In this study, anti-melanogenic, anti-inflammatory and anti-coagulant potentials of eighteen selected constituents of Ammi visnaga L. were investigated by Induced Fit Docking (IFD) and molecular dynamic simulation with Schrödinger software. The binding free energies of the selected natural compounds were computed by means of ΔG MM-GBSA studies. Anti-melanogetic activity of the constituent against agaricus bisporus tyrosinase, Priestia megaterium tyrosinase and Homo sapiens tyrosinase were evaluated. The result showed that apiumetin had more negative binding free energy against three tyrosinase enzymes than cognate ligands, tropolone and kojic acid. Docking analysis was also performed to predict the constituents with anti-inflammatory activity against human Tumor necrosis factor, Cyclooxygenase-2, Prostaglandin D2 11-ketoreductase AKR1C3 and Prostaglandin reductase PTGR2. The results showed that pyranocoumarins (visnadin, dihydrosamidin, samidin) have more negative binding free energy against Cyclooxygenase-2 and Prostaglandin D2 11-ketoreductase receptors than cognate drugs, rofecoxib and indomethacin. In addition, docking analysis shows that pyranocoumarins, apiumetin and cimifugin have more negative binding free energy against Vitamin K epoxide reductase than S-warfarin drug, predicting that they have anticoagulant activity. Furthermore, the constituents and their cognate drugs were subjected to 100 ns MD Simulation to predict their stability at the active sites of the enzymes.

Phytochemical, Morphological, and Physiological Variation in Different Ajowan (Trachyspermum ammi L.) Populations as Affected by Salt Stress, Genotype × Year Interaction and Pollination System.

In the present research, 28 populations of ajowan (Trachyspermum ammi L.) were evaluated for agro-morphological traits and essential oil yield in two consecutive years. Then, selected ajowan populations from these two years were used for further morphophysiological and biochemical studies under different salinity levels (control, 60, 90, and 120 mM NaCl). The main components of the oil were thymol (32.7-54.29%), γ-terpinene (21.71-32.81%), and p-cymene (18.74-26.16%). Salt stress caused an increase in essential oil content in the Esfahfo and Qazvin populations. The highest total phenolic and flavonoid contents were found in the Arak population grown in 60 mM NaCl (183.83 mg TAE g-1 DW) and the Yazd population grown in 90 mM NaCl (5.94 mg QE g-1 DW). Moreover, the Yazd population exhibited the strongest antioxidant activity based on DPPH (IC50 = 1566 µg/mL) under 60 mM NaCl and the highest reducing power (0.69 nm) under 120 mM NaCl. The results revealed that low and moderate salt stress improves the phytochemicals of ajowan seeds, which are useful for pharmaceutical and food applications. In this research, some morphological traits, as well as essential oil yield, were evaluated in open pollinated versus self-pollinated plants. As a result, plant height, number of flowering branches, and crown diameter significantly decreased in some populations, while a significant increase was obtained for number of flowers per umbel and seed numbers per umbel. Finally, self-pollination of ajowan might provide new insights for further breeding programs to increase oil or thymol content in ajowan.

Potential Anticancer Activity of the Furanocoumarin Derivative Xanthotoxin Isolated from Ammi majus L. Fruits: In Vitro and In Silico Studies.

Ammi majus L., an indigenous plant in Egypt, is widely used in traditional medicine due to its various pharmacological properties. We aimed to evaluate the anticancer properties of Ammi majus fruit methanol extract (AME) against liver cancer and to elucidate the active compound(s) and their mechanisms of action. Three fractions from AME (Hexane, CH2Cl2, and EtOAc) were tested for their anticancer activities against HepG2 cell line in vitro (cytotoxicity assay, cell cycle analysis, annexin V-FITC apoptosis assay, and autophagy efflux assay) and in silico (molecular docking). Among the AME fractions, CH2Cl2 fraction revealed the most potent cytotoxic activity. The structures of compounds isolated from the CH2Cl2 fraction were elucidated using 1H- and 13C-NMR and found that Compound 1 (xanthotoxin) has the strongest cytotoxic activity against HepG2 cells (IC50 6.9 ± 1.07 µg/mL). Treating HepG2 cells with 6.9 µg/mL of xanthotoxin induced significant changes in the DNA-cell cycle (increases in apoptotic pre-G1 and G2/M phases and a decrease in the S-phase). Xanthotoxin induced significant increase in Annexin-V-positive HepG2 cells both at the early and late stages of apoptosis, as well as a significant decrease in autophagic flux in cancer compared with control cells. In silico analysis of xanthotoxin against the DNA-relaxing enzyme topoisomease II (PDB code: 3QX3) revealed strong interaction with the key amino acid Asp479 in a similar fashion to that of the co-crystallized inhibitor (etoposide), implying that xanthotoxin has a potential of a broad-spectrum anticancer activity. Our results indicate that xanthotoxin exhibits anticancer effects with good biocompatibility toward normal human cells. Further studies are needed to optimize its antitumor efficacy, toxicity, solubility, and pharmacokinetics.

Assessment of Conventional Solvent Extraction vs. Supercritical Fluid Extraction of Khella (Ammi visnaga L.) Furanochromones and Their Cytotoxicity.

BACKGROUND: Khella (Ammi visnaga Lam.) fruits (Apiaceae) are rich in furanochromones, mainly khellin and visnagin, and are thus incorporated in several pharmaceutical products used mainly for treatment of renal stones. METHODS: The objective of this study was to compare the yield of khellin and visnagin obtained using different conventional solvents and supercritical fluid extraction (SCFE) with carbon dioxide (containing 5% methanol as co-solvent). Water, acetone and ethanol (30% and 95%) were selected as conventional solvents. RESULTS: Highest extract yield was obtained from 30% ethanol (15.44%), while SCFE gave the lowest yield (4.50%). However, the percentage of furanochromones were highest in SCFE (30.1%), and lowest in boiling water extract (5.95%). HPLC analysis of conventional solvent extracts showed other coumarins that did not appear in supercritical fluid extraction chromatogram due to non-selectivity of solvent extraction. Ammi visnaga extracts as well as standard khellin and visnagin were tested for their cytotoxic activity using sulforhodamine B assay on breast cancer (MCF-7) and hepatocellular carcinoma (Hep G2) cell lines. Results revealed a strong cytotoxic activity (IC50 < 20 µg/mL) for the SCFE and standard compounds (khellin and visnagin) (IC50 ranging between 12.54 ± 0.57 and 17.53 ± 1.03 µg/mL). However, ethanol and acetone extracts had moderate cytotoxic activity (IC50 20-90 µg/mL) and aqueous extract had a weak activity (IC50 > 90 µg/mL). CONCLUSIONS: Thus, supercritical fluid extraction is an efficient, relatively safe, and cheap technique that yielded a more selective purified extract with better cytotoxic activity.

Ammi Visnaga L., a Potential Medicinal Plant: A Review.

Ammi visnaga L. (Visnaga daucoides Gaertn., Family Apiaceae), also known as Khella Baldi or toothpick weed, is an annual or biennial herb indigenous to the Mediterranean region of North Africa, Asia, and Europe. The plant is known to have been used in traditional medicine a long time ago. Nowadays, it is used in modern medicine to treat many aliments such as renal colic and coronary insufficiency, and is used as an antioxidant, antifungal, and antibacterial, with a larvicidal effect on mosquito larvae. Peer-reviewed studies show that these pharmacological activities are due its valuable chemical constituents that include mainly essential oil, polyphenolic compounds including flavonoids, as well as γ-pyrones, represented mainly by khellin and visnagin. Its essential oil is reported to have antiviral, antibacterial, and larvicidal effects, while its flavonoid content is responsible for its antioxidant activity. Its γ-pyrone content has a powerful effect on facilitating the passage of kidney stones and relieving renal colic, in addition to having a relaxant effect on smooth muscle including that of the coronary arteries. The current review represents the progress in research on A. visnaga in terms of either its chemistry or biological activities. This review represents scientific support material for the use of the plant by the pharmaceutical industry.

In vitro anti-nephrotoxic potential of Ammi visnaga, Petroselinum crispum, Hordeum vulgare, and Cymbopogon schoenanthus seed or leaf extracts by suppressing the necrotic mediators, oxidative stress and inflammation.

BACKGROUND: The kidney is an essential organ required by the body to perform several important functions. Nephrotoxicity is one of the most prevailing kidney complications that result from exposure to an extrinsic or intrinsic toxicant, which increase the need for the acquisition of proper remedies. Recently, natural remedies are gaining great attention owed to the fact that they have fewer side effects than most conventional drugs. METHODS: The current study recorded a new therapeutic role of the well-known medicinal plants for kidney stones [Ammi visnaga (AVE), Petroselinum crispum (PCE), Hordeum vulgare (HVE), and Cymbopogon schoenanthus (CSE)]. Hence, the aqueous extracts of these plants examined against CCl4-induced toxicity in mammalian kidney (Vero) cells. RESULTS: These extracts showed the presence of varying amounts of phenolic and triterpenoid compounds, as well as vitamin C. Owing to the antioxidant potential of these constituents, the extracts suppressed the CCl4-induced oxidative stress significantly (p < 0.05) by scavenging the reactive oxygen species and enhancing the cellular antioxidant indices. In addition, these extracts significantly (p < 0.05) reduced the CCl4-induced inflammation by inhibiting the gene expression of NF-кB, iNOS, and in turn the level of nitric oxide. Consequently, the morphological appearance of Vero cells, cellular necrosis, and the gene expression of kidney injury molecule-1 (a marker of renal injury) after these treatments were improved. The AVE improved CCl4-induced oxidative and inflammatory stress in Vero cells and showed a more potent effect than the commonly used alpha-Ketoanalogue drug (ketosteril) in most of the studied assays. CONCLUSION: Thus, the studied plant extracts, especially AVE can be considered as promising extracts in the management of nephrotoxicity and other chronic diseases associated with oxidative stress and inflammation.

Antibacterial activity of traditional spices against lower respiratory tract pathogens: combinatorial effects of Trachyspermum ammi essential oil with conventional antibiotics.

The aim of this study was to investigate the effects of ajowan essential oil (AjEO)/thymol and antibiotics combinations against three standard strains and six resistant clinical isolates of major respiratory bacteria (Pseudomonas aeruginosa, Staphylococcus aureus and Streptococcus pneumoniae). The broth microdilution method was conducted to determine the minimum inhibitory concentrations (MIC) of essential oil/thymol and antibiotics. The checkerboard method was used to investigate the interactions between the essential oil/thymol and antibiotics by means of the fractional inhibitory concentration index (FICI). The chemical composition of essential oil was also analysed by GC-MS and GC-FID. Thymol (50·75%), γ-terpinene (25·94%) and p-cymene (18·31%) were identified as major constituents of the oil. The most sensitive organisms to ajowan volatile oil were Strep. pneumoniae bacteria (MIC = 0·125-0·5 mg ml-1 ). Synergistic effects were observed with AjEO/thymol and amoxicillin combinations on methicillin-resistant Staph. aureus clinical isolates (FICI = 0·37-0·50) and with essential oil and ciprofloxacin combinations against P. aeruginosa ATCC 27853, Staph. aureus ATCC 25923 and penicillin (P)-resistant Strep. pneumoniae bacteria (FICI = 0·37-0·50). Combination of thymol and ciprofloxacin produces synergistic effects only against P. aeruginosa ATCC 27853 and P-resistant Strep. pneumoniae clinical isolate (FICI = 0·46-0·49).

Three new coumarin types from aerial parts of Ammi majus L. and their cytotoxic activity.

Three new coumarin types were isolated from the aerial parts of the wild medicinal plant Ammi majus, which was collected from western Asia (Saudi Arabia), including pyrano coumarin, namely, 5-isobutylcoumarin-6-C-glucoside (1); furanocoumarin, namely, 6,7,9-Trimethoxy-3-(8'-methoxy-2'-oxo-2H-chromen-3-yl)-2H-furo[3,2-g]chromen-2(3H)-one (2); and pyrone coumarin, namely, 6-hydroxy-3-(2-hydroxypropyl)-7-methoxy-4 methyl coumarin (3). The structures were determined by spectroscopic methods, mainly 1D- and 2D-NMR. In vitro cytotoxicity was evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) assay. The results of cytotoxicity depending on their structure features showed that compound 3 had high activity on different cell lines, while compound 1 showed no activity against HCT116. Compound 2 had high activity towards HCT116 cell line.

Trachyspermum ammi 10 % topical cream versus placebo on neuropathic pain, a randomized, double-blind, placebo-controlled trial.

A four-week, double-blind, randomized, placebo-controlled trial was conducted to assay the effectiveness of Ajwain 10 % (Trachyspermum ammi Sprague) topical cream on neuropathic pain. Intervention encompassed Ajwain 10 % and placebo creams. Ninety-two patients who specifically mentioned daily and nocturnal burning feet were randomly assigned to receive one of those interventions. Presence and decline in patients' numbness, tingling and allodynia were also evaluated. Major outcome measure was alteration in feet burning intensity (final week versus baseline week) regarding to a visual analog scale on a 0-10 cm scale (0 being "no pain", 10 being "worst pain"). Significant reduction in feet burning scores as well as numbness, tingling and allodynia were found in Ajwain group compared to placebo. This trial examining a cream of Ajwain essential oil versus placebo revealed the significance difference between two groups. This medicament can be a good candidate for the alleviation of feet burning, a neuropathic complication.

Fast and improved separation of major coumarins in Ammi visnaga (L.) Lam. by supercritical fluid chromatography.

The first supercritical fluid chromatography method for the determination of five major coumarins (dihydrosamidin, visnadin, samidin, khellin, and visnagin) in Ammi visnaga fruits is described. Their baseline separation was possible in less than 5 min by using a UPC2 HSS C18 SB column with 1.8 µm particle size and a mobile phase comprising CO2 , methanol, acetonitrile, and diethylamine. The type of stationary phase used was of particular relevance because, except for the selected one, the others did not resolve the two structural isomers dihydrosamidin and visnadin. Method validation confirmed that the procedure is linear (R2 ≥ 0.9996) in a concentration range from 6 to 480 µg/mL, it is accurate (recovery rates: 97.2-103.6%) and precise (intraday deviation ≤ 6.6%, intraday deviation ≤ 1.7%); injecting 1 µL of standard solution, the determined limit of detection was below 1.9 µg/mL for all compounds. The analysis of different A. visnaga samples revealed their similar compositions, and khellin (0.75-1.01%) and visnagin (0.18-0.46%) were the dominant coumarins. Visnadin and dihydrosamidin, the individual quantification of which is described for the first time, were present at concentrations below 0.14%.

Larvicidal activity of extracts from Ammi visnaga Linn. (Apiaceae) seeds against Culex quinquefasciatus Say. (Diptera: Culicidae).

Efficacies of the Ammi visnaga seeds extract and a majority of substances on larval Culex quinquefasciatus mortality in various development stages including pupae were studied. The effect of exposure time on larval mortality was also studied. The effect of sublethal concentrations or short exposure times on further larval development and subsequent fecundity in adults were studied as well. Lethal doses of the extract were estimated for the 2nd, 3rd and 4th instar of C. quinquefasciatus (LC50 for 18, 23 and 180 mg L(-1), respectively). The majority of furanochromenes, khellin and visnagin, were identified by analysing the extract. Khellin was significantly more effective compared to visnagin, whose LC50 was estimated at 8, 10 and 41 mg L(-1) for the 2nd, 3rd and 4th instar larvae. Khellin showed very fast efficacy on mortality for the 3rd instar larvae in a concentration of 100 mg L(-1). Fifty percent mortality was determined 30 min after application, a time which was considerably shorter compared to the extract (113 min) or visnagin (169 min). The effect of the application of lethal concentrations on C. quinquefasciatus larval mortality was studied. The least number of adults were hatched after application of the extract and khellin (41.8% and 37.9%, respectively), less than after visnagin application (46.7%) or in the control (94.2%). LC50 application caused lower fecundity in the hatched adults, lower hatchability of the eggs, and also very low natality, more than 77% lower for khellin compared to the control. A short exposure, corresponding to our estimated LT30, caused no significant acute toxicity in the larvae (until 24 h) for the extract or visnagin (4.3% and 11.5%, respectively); however, 18 min of action from khellin caused a 54.3% mortality rate of the larvae within 24 h.

Exploring Trachyspermum ammi and Foeniculum vulgare in Hydroponic System and Compare its Chemical Constituents with Soil-Based Method: A Prospective in Agriculture.

BACKGROUND: The forthcoming problems will be of food, and soil due to environmental alteration, growing populations, pollution, and exhaustion of natural resources among other factors. Hydroponic farming has the capacity to alleviate the intimidation of these con-cerned issues in the agricultural system. Hydroponics is recommended as an alternative way to enhance product yield compared to conventional agriculture. OBJECTIVE: The present study aimed to determine the different growth parameters and constituents of soil-grown and hydroponically grown Trachyspermum ammi and Foeniculum vulgare for the first time, which could be a patentable in future. METHODS: In this study, extraction was carried out by maceration method using methanol as a solvent whereas, growth parameters were performed by the leaves number, plant height, and leaf area. Chlorophyll content was also performed in both sources. Further, a comparison of chemical constituents from different sources was analyzed by GC-MS. RESULTS: The bioactive components in hydroponically grown T. ammi were found more as compared to soil-grown T. ammi. The GC-MS analysis revealed the presence of various compounds in the methanolic extract of plant materials. CONCLUSION: Hence, hydroponics could be an alternative in agriculture and this system is now accepted globally. This method provides diverse perspectives for farmers to harvest high-yield, better quality, and enhanced bioactive compounds.

Khellin and visnagin in different organs of Ammi visnaga and Ammi majus.

Ammi visnaga and Ammi majus are plants that have long been used in traditional medicine. Nowadays, both herbs are commercially marketed as alternative medicines in different formulations. The main active ingredients of A. visnaga are known as khellin and visnagin. Information on the quantitative amounts of both bioactive substances in the different organs of the plant is lacking. This study aims to determine the amounts of these two active substances in the five organs of both plants from Turkey and provide information to the pharmaceutical industry. For this purpose, a fast and reliable micellar electrokinetic chromatography method was applied. It was found that Ammi visnaga, flowers, seeds, and leaves are good sources of both khellin and visnagin. Ammi majus only contains khellin in its seeds and flowers.

Pharmacokinetic evaluation of visnagin and Ammi visnaga aqueous extract after oral administration in rats.

The furanochromone visnagin is one of the main compounds of Ammi visnaga L. (syn. Khella) with potential effects on kidney stone prevention. After determination of the pharmacokinetic properties of visnagin after intravenous bolus administration in rats, the aim of the present study was to evaluate the pharmacokinetic properties of visnagin and an aqueous Ammi visnaga extract after oral administration in rats. In two separate experiments, three doses of visnagin (2.5, 5, and 10 mg/kg) solubilized in 25 % Captisol® and three doses of Ammi visnaga extract (standardized on visnagin and containing equivalent amounts of visnagin) were administered by oral gavage to male Sprague-Dawley rats, respectively. Plasma samples were extracted and subsequently analyzed using a validated LC-MS/MS method. Plasma concentration-time profiles were explored by non-compartmental analysis. Visnagin plasma exposure (median AUClast and AUCinf) was significantly increased for all three doses (more than 10-fold for the low dose) when administered as an extract compared to the pure agent. For both the Ammi visnaga extract and the pure compound, AUClast and AUCinf increased disproportionately with an increase in dose. Visnagin resided significantly longer in the body when given in the form of AVE with up to a three times longer median MRTlast and MRTinf for the low dose. Cmax values after AVE administration were elevated and occurred at later time points in comparison to equivalent doses of pure visnagin. The terminal half-life increased with the dose for both AVE and pure visnagin, reaching a maximum value of 1.94 h for the 10 mg/kg pure compound group.In conclusion, the exposure of visnagin is enhanced after extract administration and could result in a superior efficacy of AVE compared to an equivalent dose of visnagin.

Anti-Cancer and Anti-Inflammatory Potential of Furanocoumarins from Ammi majus L.

Secondary metabolites have potential benefits to human being. They are used in the food, agricultural and pharmaceutical industries. The secondary metabolite of furanocoumarins from different plant sources is essential in various skin-related ailments. Biologically, these chemicals are isolated from different plants in the Apiaceae, Fabaceae, Rutaceae and Moraceae families. Ammi majus L. is one of the most common plants in the family of Apiaceae with a large quantity of derivatives. The furanocoumarin derivatives defend the plant by fighting external enemies by Systemic Acquired Resistance (SAR). Via suppressing or retarding microbial growth in infected parts, these derivatives, along with SAR, help to alleviate inflammation in the human body. Latest evidence of these compounds has been established in the treatment of cancer, but the mechanism that needs to be elaborated is not yet understood. Recent studies have shown that furanocoumarin derivatives bind to DNA base pairs and block DNA replication. This may be a potential pathway that helps to regulate the growth of cancerous cells. This article reflects on the pharmaceutical data of furanocoumarins and their different mechanisms in these cases.

Thymol screening, phenolic contents, antioxidant and antibacterial activities of Iranian populations of Trachyspermum ammi (L.) Sprague (Apiaceae).

The seeds of Trachyspermum ammi were gathered at the ripening stage from different regions of Iran and grouped into 14 populations (P1-P14) accordingly. The essential oil (EO) extraction yielded in the 3.16-5% range. EOs were analyzed by gas chromatography-flame ionization detection (GC-FID) and gas chromatography-mass spectrometry (GC-MS) and 11 constituents were identified. Thymol (59.92-96.4%), p-cymene (0.55-21.15%), γ-terpinene (0.23-17.78%), and carvacrol (0.41-2.77%) were the major constituents. The highest contents of thymol and carvacrol were found in the Ghayen population (P2). Also, P2 and P8 (Estahban) had the highest value of total phenol (TPC) 43.2 mg gallic acid equivalent (GAE)/g DW, and total flavonoids (TFC) 8.03 mg quercetin equivalent (QE)/g DW, respectively. P1 (Kalat) had the highest total coumarin (TCC) value (0.26 mg coumarin equivalent CE/g DW). Based on EO constituents, principal component analysis (PCA) and cluster analysis classified populations into two chemotypes of thymol/p-cymene/γ-terpinene and thymol/carvacrol. The highest positive correlation coefficient was between α-terpinene and limonene (0.96), while the highest negative correlation was between thymol and p-cymene (-0.984). The antioxidant activities of extracts and EOs were evaluated by phosphomolybdenum (total antioxidant capacity; TAC), diphenylpicrylhydrazyl (DPPH IC50), and ferric ion reducing antioxidant power (FRAP) assays. Also, the antimicrobial activity of EOs was studied against Escherichia coli and Staphylococcus aureus. P8 with high thymol, EO content (%v/w), TFC, and antibacterial and antioxidant activities is recommended but further studies are needed to confirm the chemotype introduction.

Composition of the essential oils in various organs at different developmental stages of Ammi visnaga (L.) Lam. from Tunisia.

The composition of the essential oils isolated by hydrodistillation from various organs at different development stages of Ammi visnaga (L.) Lam. growing in Tunisia was determined by GC/MS analysis. In particular, the oil profiles of the leaves, stems, flower buds, roots, umbels, and fruits have been examined during the whole life cycle. The oil from the flowering aerial parts was characterized by a high content of isoamyl 2-methylbutanoate. After flowering and during desiccation and fructification, the umbels and fruits expressed a high content of linalool. The oils, extracted from the roots collected in the vegetatif, buds floral, and floral stages, were rich in monoterpene aldehydes, oxygenated monoterpenes, and monoterpene hydrocarbons. The highest level of non-terpene hydrocarbons was found at the flower-bud stage, represented by 61.3% of nonane. Among the monoterpenes, sabinene (12.5%) and ß-pinene (8.5%) were identified in the flower buds.

Aatrilal (Ammi majus L.), an important drug of Unani system of medicine: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Ammi majus L. (Aatrilal) a member of the family Apiaceae, is native to Egypt and widely distributed in Europe, the Mediterranean, and West Asia. It has been used for the treatment of various dermatological disorders particularly vitiligo in the Unani system of Medicine for ages. In traditional medicine, fruits are used as an emmenagogue as well as a diuretic, blood purifier and to treat leprosy, urinary and digestive disorders. AIM OF THE REVIEW: This paper aims to highlight the medicinal properties of Aatrilal in view of its temperament and phytoconstituents; to signify its potential in the treatment of vitiligo and other ailments as mentioned in Unani system of medicine and also to explore its phytochemistry, pharmacological and clinical studies. MATERIALS AND METHODS: Aatrilal was explored in classical Unani literature for its temperament (mizaj), medicinal properties and therapeutic uses. Published works available on PubMed, Science Direct, and Google Scholar were referred to collect all the available information regarding its phytochemicals and pharmacological studies. All relevant articles up to 2020 were referred including 15 classical Unani books, 15 English books, 72 research, and 3 review papers. The plant's scientific names were validated using 'The Plant List' (www.theplantlist.org). Standard Unani Medical Terminology published by Central Council for Research in Unani Medicine in collaboration with the World Health Organization was used to describe the appropriate Unani terminologies. Glossary of Indian Medicinal Plants and different indexed journals were consulted for botanical and English names. RESULTS: Aatrilal has been used in traditional medicine for ages. Due to controversies in its identity, it was adulterated and substituted with many drugs. The real identity of Aatrilal is now established as the fruit of A. majus L. Despite having numerous pharmacological activities, it is considered the first-line drug for the treatment of vitiligo. It is a rich source of furanocoumarins (xanthotoxin, also known as 8-methoxypsoralen, bergapten, imperatorin, isopimpinellin) with other compounds viz. flavonoids, terpenoids, proteins, essential oil constituents, etc. It has been reported for anti-inflammatory, analgesic, antibacterial, antiviral, cytotoxic, and many other activities. Clinical trials have shown the therapeutic potential in vitiligo and other skin disorders. CONCLUSION: Based on the available literature, it can be concluded that Aatrilal is a drug that has been effectively used in Unani system of medicine for centuries to treat the cases of vitiligo and other dermatological disorders. It has been studied extensively for its phytopharmacological properties. Raw extracts of A. majus form the crux of the main research. Many potentially bioactive compounds are included in the essential oil, but to our knowledge, no detailed studies of its biological activity are yet available. Therefore, our suggestion is to focus future research on essential oil and its ingredients.