Effect of Phytochemical Compounds on Trichomonas tenax, an Oral Protozoan.

Trichomonas tenax is an oral protozoan with an estimated global pooled prevalence of 17% in the human population.1 Observational studies have demonstrated a significant statistical correlation between oral colonization by T. tenax and the progression of periodontal disease.2 Proposed pathogenic mechanisms for this protozoan include the production of tissue-damaging enzymes, induction of apoptosis in human cells, and dysbiosis of the oral microbiome.3 In patients for whom metronidazole (MTZ) is contraindicated, phytochemicals may offer a viable alternative for controlling T. tenax. Various plant extracts have shown promising in vitro activity against other trichomonads, such as T. vaginalis and Tritrichomonas foetus, as reviewed by Friedman et al.4.

In vitro anti-Trichomonas gallinae effects of Ziziphus vulgaris L. and Camellia sinensis (L.) Kuntze extracts.

BACKGROUND: Trichomonas gallinae is a parasite that causes canker and severe loss and death, especially in young pigeons. Metronidazole (MTZ) is the recommended drug for treating avian trichomoniasis. Due to drug resistance, non-chemical alternatives, such as medicinal plant extracts, are also considered possible therapies for this disease. OBJECTIVES: This study compares the antitrichomonal effects of MTZ with extracts of Camellia sinensis and Ziziphus vulgaris on T. gallinae in vitro. METHODS: Samples of T. gallinae were taken from infected pigeons. Multi-well plates with different concentrations (5, 10, 25, 50 and 100 µg/mL) of plant extracts were used for the in vitro study. RESULTS: The minimum inhibitory concentration (MIC) of C. sinensis extract was 25 µg/mL over 24 h, compared to 50 µg/mL for MTZ. The MIC value of the Z. vulgaris extracts was 50 µg/mL. CONCLUSIONS: The results suggest that the extracts of Z. vulgaris and C. sinensis, as potential natural agents, could have anti-avian trichomoniasis properties. This study also shows that MTZ, C. sinensis and Z. vulgaris are equally effective in preventing the growth of T. gallinae trophozoites in the culture.

Antimicrobial properties of tomato leaves, stems, and fruit and their relationship to chemical composition.

BACKGROUND: We previously reported that the tomato glycoalkaloid tomatine inhibited the growth of Trichomonas vaginalis strain G3, Tritrichomonas foetus strain D1, and Tritrichomonas foetus-like strain C1 that cause disease in humans and farm and domesticated animals. The increasing prevalence of antibiotic resistance requires development of new tools to enhance or replace medicinal antibiotics. METHODS: Wild tomato plants were harvested and divided into leaves, stems, and fruit of different colors: green, yellow, and red. Samples were freeze dried and ground with a handheld mill. The resulting powders were evaluated for their potential anti-microbial effects on protozoan parasites, bacteria, and fungi. A concentration of 0.02% (w/v) was used for the inhibition of protozoan parasites. A high concentration of 10% (w/v) solution was tested for bacteria and fungi as an initial screen to evaluate potential anti-microbial activity and results using this high concentration limits its clinical relevance. RESULTS: Natural powders derived from various parts of tomato plants were all effective in inhibiting the growth of the three trichomonads to varying degrees. Test samples from leaves, stems, and immature 'green' tomato peels and fruit, all containing tomatine, were more effective as an inhibitor of the D1 strain than those prepared from yellow and red tomato peels which lack tomatine. Chlorogenic acid and quercetin glycosides were present in all parts of the plant and fruit, while caffeic acid was only found in the fruit peels. Any correlation between plant components and inhibition of the G3 and C1 strains was not apparent, although all the powders were variably effective. Tomato leaf was the most effective powder in all strains, and was also the highest in tomatine. S. enterica showed a minor susceptibility while B. cereus and C. albicans fungi both showed a significant growth inhibition with some of the test powders. The powders inhibited growth of the pathogens without affecting beneficial lactobacilli found in the normal flora of the vagina. CONCLUSIONS: The results suggest that powders prepared from tomato leaves, stems, and green tomato peels and to a lesser extent from peels from yellow and red tomatoes offer potential multiple health benefits against infections caused by pathogenic protozoa, bacteria, and fungi, without affecting beneficial lactobacilli that also reside in the normal flora of the vagina.

A review study on the anti-trichomonas activities of medicinal plants.

The parasitic diseases represent the most important health risk, especially in underdeveloped countries where they have a deep impact on public health. Trichomoniasis is a prevalent non-viral sexually transmitted disease, and a significant amount of new cases are identified each year globally. Furthermore, the infection is linked with serious concerns such as pregnancy outcomes, infertility, predisposition to cervical and prostate cancer, and increased transmission and acquisition of HIV. The therapy is restricted, adverse effects are often observed, and resistance to the drugs is emerging. Based on this, a new treatment for trichomoniasis is necessary. Natural products represent a rich source of bioactive compounds, and even today, they are used in the search for new drugs. Additionally, natural products provide a wide variety of leadership structures that can be used by the pharmaceutical industry as a template in the development of new drugs that are more effective and have fewer or no undesirable side effects compared to current treatments. This review focuses on the medicinal plants that possess anti-trichomonal activity in vitro or in vivo. An electronic database search was carried out covering the last three decades, i.e., 1990-2020. The literature search revealed that almost a dozen isolated phytoconstituents are being explored globally for their anti-trichomonal activity. Simultaneously, many countries have their own traditional or folk medicine for trichomoniasis that utilizes their native plants, as a whole, or even extracts. This review focuses mainly on the human parasite Trichomonas vaginalis. However, at some points mention is also made to Tritrichomonas foetus that causes trichomoniasis in animals of high veterinary and economical interest. We will focus on the plants and plant-based compounds and their anti-trichomonal activity. The literature search highlighted that there are abundant compounds that possess anti-trichomonal activity; however, in-depth in-vivo evaluation of compounds and their clinical evaluation has not been undertaken. There is a critical need for new anti-trichomonal compounds, and focused research on phytoconstituents can provide the way forward.

Molecular Targets Implicated in the Antiparasitic and Anti-Inflammatory Activity of the Phytochemical Curcumin in Trichomoniasis.

Trichomoniasis, is the most prevalent non-viral sexually transmitted disease worldwide. Although metronidazole (MDZ) is the recommended treatment, several strains of the parasite are resistant to MDZ, and new treatments are required. Curcumin (CUR) is a polyphenol with anti-inflammatory, antioxidant and antiparasitic properties. In this study, we evaluated the effects of CUR on two biochemical targets: on proteolytic activity and hydrogenosomal metabolism in Trichomonas vaginalis. We also investigated the role of CUR on pro-inflammatory responses induced in RAW 264.7 phagocytic cells by parasite proteinases on pro-inflammatory mediators such as the nitric oxide (NO), tumor necrosis factor α (TNFα), interleukin-1beta (IL-1ß), chaperone heat shock protein 70 (Hsp70) and glucocorticoid receptor (mGR). CUR inhibited the growth of T. vaginalis trophozoites, with an IC50 value between 117 ± 7 µM and 173 ± 15 µM, depending on the culture phase. CUR increased pyruvate:ferredoxin oxidoreductase (PfoD), hydrogenosomal enzyme expression and inhibited the proteolytic activity of parasite proteinases. CUR also inhibited NO production and decreased the expression of pro-inflammatory mediators in macrophages. The findings demonstrate the potential usefulness of CUR as an antiparasitic and anti-inflammatory treatment for trichomoniasis. It could be used to control the disease and mitigate the associated immunopathogenic effects.

Vaginitis: Review on Drug Resistance.

Female genital tract infections have a high incidence among different age groups and represent an important impact on public health. Among them, vaginitis refers to inflammation of the vulva and/or vagina due to the presence of pathogens that cause trichomoniasis, bacterial vaginosis, and vulvovaginal candidiasis. Several discomforts are associated with these infections, as well as pregnancy complications and the facilitation of HIV transmission and acquisition. The increasing resistance of microorganisms to drugs used in therapy is remarkable, since women report the recurrence of these infections and associated comorbidities. Different resistant mechanisms already described for the drugs used in the therapy against Trichomonas vaginalis, Candida spp., and Gardnerella vaginalis, as well as aspects related to pathogenesis and treatment, are discussed in this review. This study aims to contribute to drug design, avoiding therapy ineffectiveness due to drug resistance. Effective alternative therapies to treat vaginitis will reduce the recurrence of infections and, consequently, the high costs generated in the health system, improving women's well-being.

2'-Hydroxychalcones as an alternative treatment for trichomoniasis in association with metronidazole.

The treatment for trichomoniasis, based on 5'-nitroimidazol agents, has been presenting failures related to allergic reactions, side effects, and the emergence of resistant isolates. There are no alternative drugs approved for the treatment of these cases; thus, the search for new active molecules is necessary. In this scenario, chalcones have been extensively studied for their promising biological activities. Here, we presented the synthesis of three hydroxychalcones (3a, b, and c), in vitro and in silico analyses against Trichomonas vaginalis. The in vitro biological evaluation showed that hydroxychalcone 3c presented anti-T. vaginalis activity, with complete death in 12 h of incubation at minimum inhibitory concentration (MIC) of 100 µM. 3c showed a dose-dependent cytotoxicity against mammalian VERO cell line, but the association of 3c at 12.5 µM and metronidazole (MTZ) at 40 µM showed 95.31% activity against T. vaginalis trophozoites after 24 h of exposure and did not affect the VERO cell growth, appearing to be a good alternative. In silico analysis by molecular docking showed that 3c could inhibit the activity of TvMGL (methionine gamma-lyase), TvLDH (lactate dehydrogenase), and TvPNP (purine nucleoside phosphorylase) affecting the T. vaginalis survival and also suggesting a different mechanism of action from MTZ. Therefore, these results propose that hydroxychalcones are promising anti-T. vaginalis agents and must be considered for further investigations regarding trichomoniasis treatment.

Comparative effect of manuka honey on anaerobic parasitic protozoans with standard drug therapy under in vitro conditions: A preliminary study.

BACKGROUND: From the past five decades, metronidazole and tinidazole have been used for treating nonresistant and resistant giardiasis and trichomoniasis. However, due to the occurrence of drug resistance to standard therapy idealizes us to explore some additional therapies which is cost-effective, easy accessibility, and natural which has least side effects. Manuka honey obtained from Leptospermum scoparium is well known for its antibacterial and wound healing properties and is thought to be a better option as an additional therapy. OBJECTIVE: The present study was conducted to find out the effect of manuka honey on anaerobic protozoans that includes Giardia and Trichomonas under in vitro conditions in comparison to metronidazole and tinidazole. MATERIALS AND METHODS: Axenic culture of Giardia lamblia strain Portland 1 and Trichomonas vaginalis strain 413 was used for drug sensitivity assay to tinidazole, metronidazole, and manuka honey with the highest concentration of 17.1 µg/ml, 24.7 µg/ml, and 50%v/v by using (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, a tetrazole). For this, head-to-head comparison has been done and IC 50 of the standard drug as well as manuka honey was calculated. RESULTS: The result showed that percentage inhibition on the growth of both the parasites is dependent on concentration as well as exposure time of the drug. The calculated IC 50 was found to be 5.6%v/v and 1.5%v/v for manuka honey with respect to G. lamblia and T. vaginalis. CONCLUSION: The present study suggests that manuka honey can be used as an additional therapy for the patient with giardiasis or trichomoniasis. However, in vivo study in the near future will elucidate more about the effectiveness of honey in treating parasitic infections.

Potato Peels and Their Bioactive Glycoalkaloids and Phenolic Compounds Inhibit the Growth of Pathogenic Trichomonads.

Potato peel, a waste product of the potato processing industry, is high in bioactive compounds. We investigated the in vitro antitrichomonad activity of potato peel powders prepared from commercial Russet, red, purple, and fingerling varieties as well as several known potato components, alkaloids and phenolic compounds, against three pathogenic strains of trichomonads. Trichomonas vaginalis is a sexually transmitted protozoan parasite that causes the human disease trichomoniasis. Two distinct strains of the related Tritrichomonas fetus infect cattle and cats. The glycoalkaloids α-chaconine and α-solanine were highly active against all parasite lines, while their common aglycone solanidine was only mildly inhibitory. α-Solanine was several times more active than α-chaconine. The phenolic compounds caffeic and chlorogenic acids and quercetin were mildly active against the parasites. Most of the potato peel samples were at least somewhat active against all three trichomonad species, but their activities were wide-ranging and did not correspond to their glycoalkaloid and phenolic content determined by HPLC. The two Russet samples were the most active against all three parasites. The purple potato peel sample was highly active against bovine and mostly inactive against feline trichomonads. None of the test substances were inhibitory toward several normal microflora species, suggesting the potential use of the peels for targeted therapeutic treatments against trichomonads.

Antitrichomonal activity of Peganum harmala alkaloid extract against trichomoniasis in pigeon (Columba livia domestica).

1. This study was designed to evaluate the antitrichomonal effects of P. harmala alkaloid extract against T. gallinae, both in vitro and in vivo, as well as comparing it to that of metronidazole, conventional antitrichomonal medication and harmine and harmaline, the two alkaloids present in P. harmala. 2. T. gallinae were collected by the wet mount method from infected free-living pigeons. The in vitro assay was performed using multi-well plates containing test compounds in final concentrations of 5, 10, 15, 20, 30, 50 or 100 µg/ml. The in vivo assay was done on 60 experimentally infected pigeons dosed with metronidazole at 50 mg/kg body weight (BW) or alkaloids at 25 mg/kg BW. 3. The 24 h minimum inhibitory concentration (MIC) of alkaloid extract was 15 µg/ml while that of metronidazole was 50 µg/ml. Harmine and harmaline revealed 24 h MIC of 30 and 100 µg/ml, respectively. Treatment of infected pigeons with alkaloids led to a full recovery after 3 d but with metronidazole total eradication of trophozoites was not achieved. 4. In conclusion, data of the present study suggested P. harmala is a potent natural anti-trichomonal agent, effective against T. gallinae.

A sequential procedure for rapid and accurate identification of putative trichomonacidal agents.

In the current report, a sequential step-wise methodology based on in silico, in vitro and in vivo experimental procedures for the prompt detection of potential trichomonacidal drugs is proposed. A combinatorial of 12 QSAR (Quantitative Structure-Activity Relationship) models based on Linear Discrimination Analysis (LDA) are suggested for the rational identification of new trichomonacidal drugs from virtual screening of in house chemical libraries and drug databases. Subsequently, compounds selected as potential anti-trichomonas are screened in vitro against Trichomonas vaginalis. Finally, molecules with specific trichomonacidal activity are evaluated in vivo. Herein, different molecules were exposed to the proposed methodology. Firstly, the agents were virtually screened and two of the eight molecules (G-1 and dimetridazole) were classified as trichomonacidals by the 12 models. Subsequently both drugs were proved in vitro and in vivo following the workflow procedure. Although a remarkable in vitro activity was observed in both cases, dimetridazole achieved higher MIC100 activity than metronidazole against the resistant isolate. Furthermore, the in vivo models showed a remarkable reduction of lesions of more than 55% in both compounds. These observations support the current flowchart screening and suggest the use of dimetridazole as a promising drug-like scaffold for novel therapeutic alternatives against T. vaginalis resistant infections.

The antitrichomonal efficacy of garlic and metronidazole against Trichomonas gallinae infecting domestic pigeons.

Trichomonas gallinae is the causative agent of canker in pigeon. This work was carried out to investigate in the vitro and in vivo efficacy of aqueous water extract of garlic (AGE) on the growth of T. gallinae infecting pigeons compared to those of metronidazole (MTZ). MTZ and AGE were added, at different concentrations, to glucose-serum broth medium containing 1 × 10(4) trophozoites/ml. In the in vivo experiment, 48 squabs were grouped into four groups. The first group (gr. I) was not infected and not treated. Each squab of the other group was infected with 1 × 10(4) trophozoites. The second group (gr. II) was infected and not treated. On day 0, the third group (gr. III) was treated with MTZ (50 mg/kg BW) and the fourth group (gr. IV) was treated with AGE (200 mg/kg BW) for seven successive days in drinking water. In vitro study revealed that the MLC, 24, 48, and 72 h post treatment were 50, 25, and 12.5 µg/ml, respectively, for MTZ and 75, 50, and 50 mg/ml, respectively, for AGE. Garlic (200 mg/kg BW) had the highest antitrichomonal effect and shortened course of treatment of pigeons from 7 days in gr. III to 5 days. Squabs in gr. II suffered from macrocytic hypochromic anemia, whereas squabs in grs. III and IV showed normal blood pictures. Serum total protein, albumin, and globulin were increased, whereas AST, ALT, and the total cholesterol were decreased in grs. III and IV when compared to those of gr. II. Pigeons protected with AGE showed increased body weight and reduced mortality percentage than the other groups. Our results indicated that garlic may be a promising phytotherapeutic agent for protection against trichomoniasis in pigeons.

Molecular dynamic simulation and inhibitor prediction of cysteine synthase structured model as a potential drug target for trichomoniasis.

In our presented research, we made an attempt to predict the 3D model for cysteine synthase (A2GMG5_TRIVA) using homology-modeling approaches. To investigate deeper into the predicted structure, we further performed a molecular dynamics simulation for 10 ns and calculated several supporting analysis for structural properties such as RMSF, radius of gyration, and the total energy calculation to support the predicted structured model of cysteine synthase. The present findings led us to conclude that the proposed model is stereochemically stable. The overall PROCHECK G factor for the homology-modeled structure was -0.04. On the basis of the virtual screening for cysteine synthase against the NCI subset II molecule, we present the molecule 1-N, 4-N-bis [3-(1H-benzimidazol-2-yl) phenyl] benzene-1,4-dicarboxamide (ZINC01690699) having the minimum energy score (-13.0 Kcal/Mol) and a log P value of 6 as a potential inhibitory molecule used to inhibit the growth of T. vaginalis infection.

In vitro effects of various plants extracts on the growth of Trichomonas vaginalis.

Trichomoniasis is a common sexually transmitted disease (STD) caused by a protozoan parasite called Trichomonas vaginalis. This disease, with roughly 170 million new infected people worldwide per year, is associated with various problems such as pre-term delivery, high infant mortality or low birth weight. In addition, trichomoniasis increases patient susceptibility to HIV infection. The mainstay medication for trichomoniasis is metronidazole, but some resistant strains to this treatment have been identified. Moreover, treatment with metronidazole is associated with numerous side effects. Thus efforts to identify new alternative drugs in order to control trichomoniasis are vital. The use of medicinal herbs has gained widespread acceptance in both developing and non-developing societies because of owing to fewer side effects and better patient tolerance. In our search for alternative drugs in the treatment of trichomoniasis, we reviewed the effect of different plant extracts on Trichomonas vaginalis in vitro.

New antitrichomonal drug-like chemicals selected by bond (edge)-based TOMOCOMD-CARDD descriptors.

Bond-based quadratic indices, new TOMOCOMD-CARDD molecular descriptors, and linear discriminant analysis (LDA) were used to discover novel lead trichomonacidals. The obtained LDA-based quantitative structure-activity relationships (QSAR) models, using nonstochastic and stochastic indices, were able to classify correctly 87.91% (87.50%) and 89.01% (84.38%) of the chemicals in training (test) sets, respectively. They showed large Matthews correlation coefficients of 0.75 (0.71) and 0.78 (0.65) for the training (test) sets, correspondingly. Later, both models were applied to the virtual screening of 21 chemicals to find new lead antitrichomonal agents. Predictions agreed with experimental results to a great extent because a correct classification for both models of 95.24% (20 of 21) of the chemicals was obtained. Of the 21 compounds that were screened and synthesized, 2 molecules (chemicals G-1, UC-245) showed high to moderate cytocidal activity at the concentration of 10 microg/ml, another 2 compounds (G-0 and CRIS-148) showed high cytocidal activity only at the concentration of 100 microg/ml, and the remaining chemicals (from CRIS-105 to CRIS-153, except CRIS-148) were inactive at these assayed concentrations. Finally, the best candidate, G-1 (cytocidal activity of 100% at 10 microg/ml) was in vivo assayed in ovariectomized Wistar rats achieving promising results as a trichomonacidal drug-like compound.

Sexually acquired metronidazole-resistant trichomoniasis in a lesbian couple.

A lesbian couple in a monogamous relationship each presented with vaginal discharge demonstrable on culture to contain Trichomonas vaginalis. Their symptoms had failed to respond to standard regimens of metronidazole, and subsequent microbiological sensitivities confirmed resistance of the trichomonads to metronidazole (minimum inhibitory concentrations in aerobic conditions > 8 mcg/ml). In addition, the couple denied use of penetrative sex toys or recent male partners, supporting the concept of transmission through mutual masturbation.

Antitrichomonal action of emodin in mice.

Emodin, an active component contained in the root and rhizome of Rheum palmatum L. (Polygonaceae), was found to have an inhibitory effect on the pathogenicity of Trichomonas vaginalis in mice. Emodin delayed the development of subcutaneous abscesses due to infection of this parasite. Also, it cures the intravaginal infection of trichomonads through oral administration. In cell cultures, it reduced the cytotoxic effect of this parasite towards mammalian cells. This inhibition was markedly reversed by the coexistence of free radical scavengers, indicating the possible mediation of free radicals.

[Ofloxacin and ciprofloxacin in the treatment of sexually-transmitted diseases]. / Ofloksatsin i tsiprofloksatsin v terapii infektsii, peredavaemykh polovym putem.

A complex clinico-laboratory++ examination and treatment were made of 76 women with inflammatory processes in the urogenital tract. Gonorrhea, trichomoniasis, chlamydiosis and Ureaplasma infection were detected in 60, 31.4, 41 and 14 per cent of the cases, respectively. There were affections of the rectum by gonococci, chlamydia, ureaplasmas and Trichomonas in 55, 32, 10.6 and 6.6 per cent of the cases, respectively. The frequency of chlamydia in the oropharynx amounted to 30 per cent whereas gonococci and ureaplasma were less frequent i.e. 9 and 1.2 per cent, respectively. The combination of the above pathogens in the rectum were the following: gonococci and chlamydia (15 per cent of the cases), gonococci, chlamydia and Trichomonas (7.3 per cent), gonococci and ureaplasma (7.3 per cent), ureaplasma and chlamydia (7.8 per cent). In the throat the association of gonococci and chlamydia was detected in 3.7 per cent of the cases. It should be indicated that the signs of sex-transmitted diseases were few, which required careful clinico-laboratory examination of the extragenital foci in the patients with inflammatory urogenital diseases. Ofloxacin showed a high efficacy in the treatment of patients with gonorrhea and ureaplasmosis. Its use in treatment of chlamydiosis proved inexpedient while ciprofloxacin was effective in the treatment of the infection.

The use of metronidazole, tinidazole and dimetridazole in eliminating trichomonads from laboratory mice.

Metronidazole, tinidazole and dimetridazole were administered in the drinking water for 5 days to mice experimentally infected with Tritrichomonas muris and Tetratrichomonas microta. Mice were successfully infected with T. muris and T. microta recovered from infected gerbils. The trichomonas infection was successfully eliminated in mice given a 1% sucrose solution containing 2.5 mg/ml metronidazole or tinidazole. Mice receiving 1.0 mg/ml metronidazole, 1.0 mg/ml tinidazole and 1.2, 5.0 and 10.0 mg/ml dimetridazole failed to eliminate the trichomonas organism. A reduction in water intake was only noted with mice receiving 10 mg/ml dimetridazole. In mice receiving only 1% sucrose the infection was not eliminated.