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Pomegranate flower extract diminishes cardiac fibrosis in Zucker diabetic fatty rats: modulation of cardiac endothelin-1 and nuclear factor-kappaB pathways.

The diabetic heart shows increased fibrosis, which impairs cardiac function. Endothelin (ET)-1 and nuclear factor-kappaB (NF-kappaB) interactively regulate fibroblast growth. We have recently demonstrated that Punica granatum flower (PGF), a Unani anti-diabetic medicine, is a dual activator of peroxisome proliferator-activated receptor (PPAR)-alpha and -gamma, and improves hyperglycemia, hyperlipidemia, and fatty heart in Zucker diabetic fatty (ZDF) rat, a genetic animal model of type 2 diabetes and obesity. Here, we demonstrated that six-week treatment with PGF extract (500 mg/kg, p.o.) in Zucker diabetic fatty rats reduced the ratios of van Gieson-stained interstitial collagen deposit area to total left ventricular area and perivascular collagen deposit areas to coronary artery media area in the heart. This was accompanied by suppression of overexpressed cardiac fibronectin and collagen I and III mRNAs. Punica granatum flower extract reduced the up-regulated cardiac mRNA expression of ET-1, ETA, inhibitor-kappaBbeta and c-jun, and normalized the down-regulated mRNA expression of inhibitor-kappaBalpha in Zucker diabetic fatty rats. In vitro, Punica granatum flower extract and its components oleanolic acid, ursolic acid, and gallic acid inhibited lipopolysaccharide-induced NF-kappaB activation in macrophages. Our findings indicate that Punica granatum flower extract diminishes cardiac fibrosis in Zucker diabetic fatty rats, at least in part, by modulating cardiac ET-1 and NF-kappaB signaling.

Animals↗

Evolutionary vestigialization of sex in a clonal plant: selection versus neutral mutation in geographically peripheral populations.

The loss of traits that no longer contribute to fitness is widespread; however, the causative evolutionary mechanisms are poorly understood. Vestigialization could proceed through the fixation of selectively neutral degenerative mutations via genetic drift. Alternatively, selection may facilitate vestigialization if trait loss results in enhanced fitness. We tested these hypotheses using Decodon verticillatus, a clonal plant in which sexual sterility has arisen repeatedly in populations across the northern geographical range limit. We compared growth and survival of replicated genotypes from 7 sexually fertile and 18 sterile populations, over 3 years in a common environment. Survival of sterile genotypes was 53% greater than for fertile genotypes, but there was no difference in biomass accumulation. Almost all mortality, and hence increased performance of sterile genotypes, occurred during simulated overwinter dormancy. These observations suggest that selection has facilitated the vestigialization of sex, and thus do not support the neutral mutation hypothesis. The selective mechanism probably involves the relaxation of a genetic trade-off between sexual reproduction and survival: alleles that increase vegetative performance at the expense of sexual fertility are selected in geographically peripheral populations where sexual reproduction is suppressed by adverse environmental conditions.

Analysis of Variance↗

A new genus of the family Micromonosporaceae, Polymorphospora gen. nov., with description of Polymorphospora rubra sp. nov.

Two actinomycete strains were isolated from soil surrounding mangrove roots. The isolates formed short spore chains with spores showing diverse shapes. The isolates contained glutamic acid, glycine, alanine and meso-diaminopimelic acid in the cell wall, 3-O-methylmannose, mannose, galactose and glucose as the whole-cell sugars and MK-10(H(6)), MK-10(H(4)), MK-9(H(6)) and MK-9(H(4)) as the predominant isoprenoid quinones. The isolates formed a distinct taxon in the phylogenetic tree of the Micromonosporaceae based on analysis of 16S rRNA gene sequences and showed chemical and phenotypic properties that were different from members of all of the other genera of this family. Based on these observations, it is proposed that the novel isolates belong to a new genus, Polymorphospora gen. nov. The type species of the genus is proposed as Polymorphospora rubra sp. nov., with strain TT 97-42(T) (=NBRC 101157(T)=DSM 44947(T)) as the type strain.

Actinobacteria↗

Optimization of aquatic-terrestrial ecosystem in relation to soil nitrogen status for the cultivation of fish and aquatic food crops of the Indian subtropics.

A case study was undertaken during wet and postwet seasons to improve the perennial and alternate submerged saucer-shaped ponded lands (tal and semi-tal lands) in the coasts and northeastern plains of the Indian subtropics through pisciculture and cultivation of starch- and protein-rich aquatic food crops like water chestnut (Trapa bispinosa Roxb.) and makhana or fox nut (Euryale ferox Salisb.). The study revealed that the physico-chemical properties of soils (pH, organic C, organic matter, available N, P, and K) as well as quality of water (pH, EC, BOD, COD, CO3 +, HCO3-, NO3-N, SO4-S-, and Cl-), growing fish, makhana, and water chestnut was remarkably influenced by different moisture regimes and exhibited a significant improvement of soil health. The amount of organic C, available N, P, and K content were found significantly highest in the treatment where makhana was grown under alternate flooding and drying situation with a depth >2 m as compared to other treatments. Such enrichment of soil fertility, particularly in available N and P content, might be due to the accumulation of considerable amounts of biomass and fish excreta and their subsequent decomposition in situ in the soils. Therefore, the present study suggests that the N-enriched soil may effectively be utilized further for growing subsequent arable crops surroundings during summer season, which not only saves the amount of applied N fertilizer but also increases the apparent N efficiency with simultaneous increase in yield, and would benefit the farmers in this region.

Animals↗

Pomegranate seed oil rich in conjugated linolenic acid suppresses chemically induced colon carcinogenesis in rats.

Pomegranate (Punica granatum L.) seed oil (PGO) contains more than 70% cis(c)9,trans(t)11,c13-18:3 as conjugated linolenic acids (CLN). Our previous short-term experiment demonstrated that seed oil from bitter melon (Momordica charantia) (BMO), which is rich in c9,t11,t13-CLN, inhibited the occurrence of colonic aberrant crypt foci (ACF) induced by azoxymethane (AOM). In this study, we investigated the effect of dietary PGO on the development of AOM-induced colonic malignancies and compared it with that of conjugated linoleic acid (CLA). To induce colonic tumors, 6-week old male F344 rats were given subcutaneous injections of AOM (20 mg/kg body weight) once a week for 2 weeks. One week before the AOM treatment they were started on diet containing 0.01%, 0.1%, or 1% PGO or 1% CLA for 32 weeks. Upon termination of the bioassay (32 weeks) colon tumors were evaluated histopathologically. AOM exposure produced colonic adenocarcinoma with an incidence of 81% and multiplicity of 1.88 +/- 1.54 at week 32. Administration of PGO in the diet significantly inhibited the incidence (AOM + 0.01% PGO, 44%, P < 0.05; AOM + 0.1% PGO, 38%, P < 0.01; AOM + 1% PGO, 56%) and the multiplicity (AOM + 0.01% PGO, 0.56 +/- 0.73, P < 0.01; AOM + 0.1% PGO, 0.50 +/- 0.73, P < 0.005; AOM + 1% PGO, 0.88 +/- 0.96, P < 0.05) of colonic adenocarcinomas, although a clear dose-response relationship was not observed at these dose levels. CLA feeding also slightly, but not significantly, reduced the incidence and multiplicity of colonic adenocarcinomas. The inhibition of colonic tumors by PGO was associated with an increased content of CLA (c9,t11-18:2) in the lipid fraction of colonic mucosa and liver. Also, administration of PGO in the diet elevated expression of peroxisome proliferator-activated receptor (PPAR) gamma protein in the non-tumor mucosa. These results suggest that PGO rich in c9,t11,c13-CLN can suppress AOM-induced colon carcinogenesis, and the inhibition is associated in part with the increased content of CLA in the colon and liver and/or increased expression of PPARgamma protein in the colon mucosa.

Animals↗

Anaphylaxis to excipient mannitol: evidence for an immunoglobulin E-mediated mechanism.

BACKGROUND: Anaphylaxis to mannitol present naturally in pomegranate and cultivated mushroom in a sensitized subject has been described recently, and an IgE-mediated mechanism to this sugar alcohol has been proposed. The same subject also experienced severe allergic reactions to a chewable pharmaceutical (cisapride drug). OBJECTIVE: The purpose of the study was to identify allergenic component in the pharmaceutical preparation, and also, to understand the mechanism of immediate hypersensitivity to mannitol. METHODS: Methodology involved skin prick tests (SPTs), high-performance liquid chromatographic (HPLC) analysis of pharmaceutical preparations, separation of mannitol by Ca++-ion-moderated cation-exchange chromatography, preparation of alditol-protein conjugates by reductive amination, SPT using the conjugates, hapten affinity purification of the allergic serum on D-mannitol-keyhole limpet haemocyanin (KLH)-Sepharose CL-6B, and detection of serum mannitol-specific IgE by ELISA. RESULTS: Component testing by SPT, and HPLC analysis of various pharmaceuticals indicated that the excipient mannitol is the causative allergen. Mannitol separated from Cisapid MPS showed allergenic activity by SPT. Among the several conjugates tested by SPT, D-mannitol-bovine serum albumin and D-mannitol-KLH showed positive weal/flare reaction, demonstrating the presence of cell-bound mannitol-specific IgE in vivo. Negative results with D-glucitol, D-galactitol, meso-erythritol, and L-mannitol protein conjugates clearly showed that the mannitol-specific human IgE is very specific to the D-isomer of mannitol. ELISA using the hapten affinity-purified allergic serum was positive, demonstrating the presence of mannitol-specific serum IgE in the allergic subject. CONCLUSION: Mannitol, which is widely used as a food and drug additive (excipient), can rarely cause IgE-mediated anaphylaxis. This study is the first one to demonstrate the presence of mannitol-specific human IgE in a sensitized allergic subject to validate an IgE-mediated hypersensitivity mechanism for mannitol.

Adult↗

Activity of medicinal plant extracts against hospital isolates of methicillin-resistant Staphylococcus aureus.

Aqueous and ethanolic extracts of ten traditional Thai medicinal plants were investigated for their ability to inhibit 35 hospital isolates of methicillin-resistant Staphylococcus aureus (MRSA). Nine medicinal plants displayed activity against all isolates tested. Ethanolic extracts of Garcinia mangostana, Punica granatum and Quercus infectoria were most effective, with MICs for MRSA isolates of 0.05-0.4, 0.2-0.4 and 0.2-0.4 mg/mL, respectively, and for S. aureus ATCC 25923 of 0.1, 0.2 and 0.1 mg/mL, respectively. MBCs for MRSA isolates were 0.1-0.4, 1.6-3.2 and 0.4-1.6 mg/mL, and for S. aureus ATCC 25923 were 0.4, 3.2 and 1.6 mg/mL, respectively.

Ethanol↗

Pigments, photosynthesis and photoinhibition in two amphibious plants: consequences of varying carbon availability.

In the present study, we investigated the effects of CO(2) availability on photosynthesis, photoinhibition and pigmentation in two species of amphibious plants, Lobelia cardinalis and Nesaea crassicaulis. The plants were grown emergent under atmospheric conditions and submerged under low and high CO(2) availability. Compared with Lobelia, Nesaea had thin leaves and few stomata in all CO(2) treatments. While Lobelia expressed no variation in anthocyanin content among treatments, Nesaea produced high concentrations of anthocyanin when submerged. Lobelia photosynthesis increased in response to increasing CO(2) availability, and photoinhibition was negatively related to xanthophyll content. By contrast, Nesaea photosynthesis was highest under submerged conditions, and there was no relationship between photoinhibition and the xanthophyll content. We conclude that the response of Lobelia to varying CO(2) availability is similar to that of terrestrial plants and that this species relies on the xanthophyll cycle for nonphotochemical quenching (NPQ) and protection against photoinhibition. By contrast, the thin leaves, few stomata and low levels of chlorophylls and accessory pigments in Nesaea, relative to Lobelia, suggest adaptation to a submerged habitat. While Nesaea does not seem to rely on the xanthophyll cycle or other xanthophylls for NPQ, some role of anthocyanins in the protection against photoinhibition cannot be ruled out, owing to its effect as a sunscreen and as an efficient quencher of free radicals.

Anthocyanins↗

Inhibition of aflatoxin B production of Aspergillus flavus, isolated from soybean seeds by certain natural plant products.

AIMS: The inhibitory effect of cowdung fumes, Captan, leaf powder of Withania somnifera, Hyptis suaveolens, Eucalyptus citriodora, peel powder of Citrus sinensis, Citrus medica and Punica granatum, neem cake and pongamia cake and spore suspension of Trichoderma harzianum and Aspergillus niger on aflatoxin B(1) production by toxigenic strain of Aspergillus flavus isolated from soybean seeds was investigated. METHODS AND RESULTS: Soybean seed was treated with different natural products and fungicide captan and was inoculated with toxigenic strain of A. flavus and incubated for different periods. The results showed that all the treatments were effective in controlling aflatoxin B(1) production. Captan, neem cake, spore suspension of T. harzianum, A. niger and combination of both reduced the level of aflatoxin B(1) to a great extent. Leaf powder of W. somnifera, H. suaveolens, peel powder of C. sinensis, C. medica and pongamia cake also controlled the aflatoxin B(1) production. CONCLUSIONS: All the natural product treatments applied were significantly effective in inhibiting aflatoxin B(1) production on soybean seeds by A. flavus. SIGNIFICANCE AND IMPACT OF THE STUDY: These natural plant products may successfully replace chemical fungicides and provide an alternative method to protect soybean and other agricultural commodities from aflatoxin B(1) production by A. flavus.

Aflatoxin B1↗

Assessing the therapeutic use of Lafoensia pacari St. Hil. extract (mangava-brava) in the eradication of Helicobacter pylori: double-blind randomized clinical trial.

BACKGROUND: The eradication of Helicobacter pylori is easily achieved by combining antisecretory agents and antibiotics; however, the cost of these associations is very high for the population of Third World countries, where the prevalence of the infection is even higher and leads to markedly reduced treatment effectiveness. We tested a plant (Lafoensia pacari) that is used in the central region of Brazil. According to previous studies, this plant has high concentrations of ellagic acid, which presents gastric antisecretory and antibacterial actions. MATERIAL AND METHODS: One hundred dyspeptic, urease-positive patients were randomized to receive 500 mg of methanolic extract of L. pacari (n = 55) or placebo (n = 45), for 14 days, in a double-blind clinical trial. The main variables assessed were the eradication of H. pylori 8 weeks after the intervention and complete symptom relief at the end of the treatment. RESULTS: The examinations (urease and histology) showed persistence of H. pylori in 100% of participants. Complete symptom relief was experienced by 42.5% of patients (95% CI: 29.4-55.8) in the intervention group and by 21% (95% CI: 8.8-33.1) in the control group, p = .020. The side-effects were minimal and similar in both groups. CONCLUSIONS: The extract of L. pacari as a single agent was not effective to eradicate H. pylori. However, it was well tolerated and many participants reported relief of symptoms. Future studies may test the agent using larger doses and longer periods, in monotherapy or in combination with antibiotics.

Adult↗

Botanical antioxidants in the prevention of photocarcinogenesis and photoaging.

Exposure of the skin to ultraviolet (UV) radiation, particularly its UV-B component (280-320 nm), from the sun results in erythema, edema, hyperplasia, hyperpigmentation, sunburn cells, immunosuppression, photoaging, and skin cancer. Amongst these various adverse effects of UV-B radiation, skin cancer and photoaging are of great concern. More recent changes in lifestyle have led to a significant increase in the amount of UV-B radiation people receive leading to a surge in the incidence of skin cancer and photoaging. As these trends are likely to continue in the foreseeable future, the adverse effect of UV-B has become a major human health concern. Therefore, development of novel strategies to reduce the occurrence of skin cancer and delay the process of photoaging are highly desirable goals. One approach to reduce their occurrence is through photochemoprevention, which we define as the use of agents capable of ameliorating the adverse effects of UV-B on the skin. Photochemoprevention via use of botanical antioxidants, present in the common diet of human have gained considerable attention as photochemopreventive agents for human use. Many such agents have also found a place in skin care products. This review will focus on the effects of selected botanical antioxidants in the prevention of photocarcinogenesis and photoaging.

Antioxidants↗

Genomic resequencing unravels species differentiation and polyploid origins in the aquatic plant genus Trapa.

Trapa L. is a non-cereal aquatic crop with significant economic and ecological value. However, debates over its classification have caused uncertainties in species differentiation and the mechanisms of polyploid speciation. This study employed whole-genome resequencing together with the fruit morphology of 229 Trapa accessions (153 Asian and 76 North American samples) to elucidate species differentiation and polyploidization events in Trapa. For the species with AA genome and large fruits, clear genetic differentiation was found between two clades with different geographic origins, that is, from the Yangtze River and Amur River basins. The invasive AA species in North America (T. natans) was identified as originating from the Amur River based on genetic and morphological similarities, while all the cultivated accessions were AA species originating from the Yangtze River with severe genetic impoverishment. The separation of the two BB species with small seeds, that is, T. incisa and T. maximowiczii, was strongly supported by both morphological and genetic evidence. For the tetraploids, Asian and North American tetraploids were revealed to have distinct evolutionary origins. Asian allotetraploids (AABB) originated through hybridization between AA diploids from the Yangtze River Basin and BB diploids T. maximowiczii, supported by nuclear and chloroplast evidence. In contrast, the invasive North American tetraploids (T. bispinosa var. iinumai) exhibited an AACC-like genome, suggesting an independent polyploidization involving an unknown "CC" diploid. These findings provide critical insights into Trapa's complex evolutionary history, polyploidizations, and invasive origins, offering a genomic foundation for the conservation and sustainable utilization of the underutilized aquatic crop amid global environmental challenges.

Polyploidy↗

Effects of pomegranate juice on human cytochrome p450 3A (CYP3A) and carbamazepine pharmacokinetics in rats.

In this study, we investigated whether components of pomegranate could inhibit CYP3A-mediated drug metabolism. The ability of pomegranate to inhibit the carbamazepine 10,11-epoxidase activity of CYP3A was examined using human liver microsomes, and pomegranate juice was shown to be a potent inhibitor of human CYP3A. Addition of 25 microl (5.0% v/v) of pomegranate juice resulted in almost complete inhibition of the carbamazepine 10,11-epoxidase activity of human CYP3A (1.8%). The inhibition potency of pomegranate juice was similar to that of grapefruit juice. In addition, we investigated the in vivo interaction between pomegranate juice and carbamazepine pharmacokinetics using rats. In comparison with water, the area under the concentration-time curve (AUC) of carbamazepine was approximately 1.5-fold higher when pomegranate juice (2 ml) was orally injected 1 h before the oral administration of the carbamazepine (50 mg/kg). On the other hand, the elimination half-life of carbamazepine and the AUC ratio of carbamazepine 10,11-epoxide to carbamazepine were not altered by the injection of pomegranate juice. These data suggest that pomegranate juice component(s) impairs the function of enteric but not hepatic CYP3A. Thus, we discovered that a component(s) of pomegranate inhibits the human CYP3A-mediated metabolism of carbamazepine. Furthermore, pomegranate juice alters the carbamazepine pharmacokinetics in rats.

Animals↗

Effects of pomegranate juice on human cytochrome P450 2C9 and tolbutamide pharmacokinetics in rats.

In this study, we investigated whether pomegranate juice could inhibit CYP2C9 activity. The ability of pomegranate juice to inhibit the diclofenac 4'-hydroxylase activity of human CYP2C9 was examined using human liver microsomes. Pomegranate juice was shown to be a potent inhibitor of human CYP2C9. The addition of 25 microl (5% v/v) of pomegranate juice resulted in almost complete inhibition of human CYP2C9 activity. In addition, we investigated the effect of pomegranate juice on the pharmacokinetics of tolbutamide (substrate for CYP2C9) in rats. Relative to the control group, the area under the concentration-time curve was approximately 1.2-fold greater when pomegranate juice (3 ml) was injected p.o. 1 h before the p.o. administration of the tolbutamide (20 mg/kg). The elimination half-life of tolbutamide was not altered by pomegranate juice administration. These results suggest pomegranate juice ingestion inhibits the intestinal metabolism of tolbutamide without inhibiting the hepatic metabolism in rats. Thus, we discovered that pomegranate juice inhibited human CYP2C9 activity and furthermore increased tolbutamide bioavailability in rats.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Potent inhibition by star fruit of human cytochrome P450 3A (CYP3A) activity.

There has been very limited information on the capacities of tropical fruits to inhibit human cytochrome P450 3A (CYP3A) activity. Thus, the inhibitory effects of tropical fruits on midazolam 1'-hydroxylase activity of CYP3A in human liver microsomes were evaluated. Eight tropical fruits such as common papaw, dragon fruit, kiwi fruit, mango, passion fruit, pomegranate, rambutan, and star fruit were tested. We also examined the inhibition of CYP3A activity by grapefruit (white) and Valencia orange as controls. The juice of star fruit showed the most potent inhibition of CYP3A. The addition of a star fruit juice (5.0%, v/v) resulted in the almost complete inhibition of midazolam 1'-hydroxylase activity (residual activity of 0.1%). In the case of grape-fruit, the residual activity was 14.7%. The inhibition depended on the amount of fruit juice added to the incubation mixture (0.2-6.0%, v/v). The elongation of the preincubation period of a juice from star fruit (1.25 or 2.5%, v/v) with the microsomal fraction did not alter the CYP3A inhibition, suggesting that the star fruit did not contain a mechanism-based inhibitor. Thus, we discovered filtered extracts of star fruit juice to be inhibitors of human CYP3A activity in vitro.

Actinidia↗

Synergic interaction between pomegranate extract and antibiotics against Staphylococcus aureus.

We evaluated the interaction between Punica granatum (pomegranate) methanolic extract (PGME) and antibiotics against 30 clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA). Susceptibility testing of the isolates to PGME and antibiotics was performed by the broth dilution method. Synergic activity was detected between PGME and the 5 antibiotics tested, chloramphenicol, gentamicin, ampicillin, tetracycline, and oxacillin, ranging from 38% to 73%. For some isolates, PGME did not interfere with the action of any of the antibiotics tested. The bactericidal activity of PGME (0.1 x MIC) in combination with ampicillin (0.5 x MIC) was assessed using chosen isolates by time-kill assays, and they confirmed the synergic activity. Using this combination, cell viability was reduced by 99.9% and 72.5% in MSSA and MRSA populations, respectively. PGME increased the post-antibiotic effect (PAE) of ampicillin from 3 to 7 h. In addition, PGME demonstrated the potential to either inhibit the efflux pump NorA or to enhance the influx of the drug. The detection of in vitro variant colonies of S. aureus resistant to PGME was low and they did not survive. In conclusion, PGME dramatically enhanced the activity of all antibiotics tested, and thus, offers an alternative for the extension of the useful lifetime of these antibiotics.

Anti-Bacterial Agents↗

Phase II study of pomegranate juice for men with rising prostate-specific antigen following surgery or radiation for prostate cancer.

PURPOSE: Phytochemicals in plants may have cancer preventive benefits through antioxidation and via gene-nutrient interactions. We sought to determine the effects of pomegranate juice (a major source of antioxidants) consumption on prostate-specific antigen (PSA) progression in men with a rising PSA following primary therapy. EXPERIMENTAL DESIGN: A phase II, Simon two-stage clinical trial for men with rising PSA after surgery or radiotherapy was conducted. Eligible patients had a detectable PSA > 0.2 and < 5 ng/mL and Gleason score < or = 7. Patients were treated with 8 ounces of pomegranate juice daily (Wonderful variety, 570 mg total polyphenol gallic acid equivalents) until disease progression. Clinical end points included safety and effect on serum PSA, serum-induced proliferation and apoptosis of LNCaP cells, serum lipid peroxidation, and serum nitric oxide levels. RESULTS: The study was fully accrued after efficacy criteria were met. There were no serious adverse events reported and the treatment was well tolerated. Mean PSA doubling time significantly increased with treatment from a mean of 15 months at baseline to 54 months posttreatment (P < 0.001). In vitro assays comparing pretreatment and posttreatment patient serum on the growth of LNCaP showed a 12% decrease in cell proliferation and a 17% increase in apoptosis (P = 0.0048 and 0.0004, respectively), a 23% increase in serum nitric oxide (P = 0.0085), and significant (P < 0.02) reductions in oxidative state and sensitivity to oxidation of serum lipids after versus before pomegranate juice consumption. CONCLUSIONS: We report the first clinical trial of pomegranate juice in patients with prostate cancer. The statistically significant prolongation of PSA doubling time, coupled with corresponding laboratory effects on prostate cancer in vitro cell proliferation and apoptosis as well as oxidative stress, warrant further testing in a placebo-controlled study.

Administration, Oral↗