Isoliquiritigenin: a potential drug candidate for the management of erectile dysfunction.

OBJECTIVE: This study aimed to assess the erectogenic properties of isoliquiritigenin taking sildenafil (SDF) as the standard. METHODS: The binding affinity of isoliquiritigenin (ISL) with the erectile marker proteins (endothelial nitric oxide synthase [eNOS] and enzyme phosphodiesterase type 5 [PDE5]) was investigated using Autodock Vina, which was validated using molecular dynamics simulation. Furthermore, the effect of ISL on the eNOS and PDE5 messenger ribonucleic acid (mRNA) expression and the sexual behavior of mice was investigated, along with the assessment of the pharmacokinetics of ISL. KEY FINDINGS: The results revealed that the binding affinity of ISL-eNOS/PDE5 and SDF-eNOS/PDE5 was in the range of -7.5 to -8.6 kcal/mol. The ISL-eNOS/PDE5 complexes remained stable throughout the 100 ns simulation period. Root mean square deviation, Rg, SASA, hydrogen, and hydrophobic interactions were similar between ISL-eNOS/PDE5 and SDF-eNOS/PDE5. Analysis of mRNA expressions in paroxetine (PRX)-induced ED mice showed that the co-administration of PRX with ISL reduced PDE5 and increased eNOS mRNA expression, similar to the co-administered group (PRX+SDF). The sexual behavior study revealed that the results of PRX+ISL were better than those of the PRX+SDF group. Pharmacokinetic evaluation further demonstrated that ISL possesses drug-like properties. CONCLUSIONS: The results showed that ISL is equally potent as SDF in terms of binding affinity, specific pharmacological properties, and modulating sexual behavior.

Isoliquiritigenin ameliorates paroxetine-induced sexual dysfunction in male albino mice.

Paroxetine (PRX), a widely prescribed antidepressant, often leads to sexual dysfunction. The available management options such as sildenafil (SDF), are associated with side effects. The present study investigates the fertility-boosting properties of isoliquiritigenin (ISL) on PRX-induced sexual dysfunction in male mice. We allocated fertile mice into six different groups (n = 5): group I- DMSO; group II- PRX; group III- co-administered PRX and SDF; group IV- ISL alone; group V- co-administered PRX and ISL (low dose); and, group VI- co-administered PRX and ISL (high dose). 14 days post treatment, animals were sacrificed, and the weights of the testis and epididymis were evaluated. Furthermore, sperm parameters, testicular and epididymal antioxidant levels, serum testosterone and nitric oxide (NO) levels, histoarchitecture of testis and epididymis, and markers of cellular toxicity were assessed. Results revealed that the PRX administration reduced organ weights, sperm count, intact acrosome, catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), serum testosterone, and NO levels, and increased sperm abnormalities and MDA levels (a biomarker for lipid peroxidation). Additionally, we observed damage in the testis and epididymis. The toxicity biomarker study revealed a higher concentration of SGOT, SGPT, and ALP enzymes in the PRX-treated group. However, the co-administration of PRX with ISL ameliorated the adverse effect of PRX on the parameters mentioned above. The PRX+ISL (high) results were almost at par with the PRX+SDF group. The group that received ISL alone showed overall improvements. In conclusion, our comprehensive panel of tests indicates that ISL could be helpful in managing sexual dysfunction.

Fertility regulatory potential of Persicaria hydropiper (L.) Delarbre methanolic root extract in female albino mice: An insight into the phytochemicals present and role of the extract in contraception.

People from some parts of the world traditionally depend on different herbal medicines for fertility regulation. The Mishing women of Assam, India have been using the dry root powder of Persicaria hydropiper for years as a birth control medicine. The present study was designed to investigate the chemical composition of methanolic extract from the dry roots of P. hydropiper as well as to study its anti-implantation effect. P. hydropiper roots were collected from paddy fields and the methanolic extract was prepared using dry powdered roots. Gas chromatography-mass spectrometry (GCMS) analysis of the methanolic root extract was performed for phytochemical analysis. The estrous cycle of the female mice was monitored by observation of the cells in the vaginal smear. The estrogenic and anti-implantation effect was observed using routine histological procedures with Haematoxylin & Eosin staining performed in mice. Total serum cholesterol level was also measured. The GCMS analysis revealed the presence of stigmasterol and 3-deoxyestradiol, which are known to possess antifertility properties. The extract (1000 mg/kg bodyweight dose) altered the duration and sequence of the estrous cycle of cyclic females with a prolonged metestrous of 2 days, followed by an early estrous. There was hyperplasia in the endometrial epithelium and even shedding of the same on high duration treatment on day 6. There was a significant (p < 0.05) rise in total cholesterol levels in the treated groups. The highest rise was observed in the day 1 group (from 67.91 ± 1.98 to 147.53 ± 3.20 mg/dl) while the lowest change was there in the day 2 group (from 78.76 ± 2.04 to 103.26 ± 2.34 mg/dl). The presence of compounds like stigmasterol and 3-deoxyestradiol with profound antifertility properties possibly has an influence on the molecular pathway for embryo implantation. The changes in uterine histoarchitecture in the form of uterine hyperplasia on treatment with the extract point out towards the effect of the estrogenic compounds. Such implantation preventing results provides support to the traditional belief and opens the door for new drug discovery for reproduction regulation. A detailed molecular study is necessary in this regard.

A review on the ethnopharmacology, phytochemistry and pharmacology of Polygonum hydropiper Linn.

OBJECTIVES: Polygonum hydropiper is a herb with worldwide distribution, having tremendous value as traditional medicine among different communities. It is used to cure many kinds of ailments such as gynaecological disorders, ulcer, anxiety, pain, cancer, etc. The present review gives emphasis on a thorough and updated study of the botanical description and taxonomy, distribution, habitat, ethnopharmacology, phytochemical constituents, pharmacological activities and toxicological aspects of P. hydropiper. METHODS: The information included in this review was collected from different scientific databases like PubMed, ScienceDirect, Google Scholar, etc. In addition to the botanical description and taxonomy, lots of ethnomedicinal use of the water-pepper plant could be found. RESULT: A good number of compounds belonging to the categories like alkaloids, carbohydrates, flavonoids, etc. were confirmed to be present in the plant. Moreover, in different studies, this plant was found to possess activities like anti-Alzheimer, antibacterial, antidementia, antifertility, neuropharmacological, sedative, anxiolytic, thrombolytic and membrane-stabilizing activity, etc. with minimal toxicity. CONCLUSION: These properties may be directly related to its possession of a large number of bioactive molecules of different categories. Based on these properties, isolation of responsible compound(s), evaluation of molecular mechanisms of their action and clinical trials are recommended.

Efficacy of topical application of 0.03% tacrolimus eye ointment in the management of allergic conjunctivitis.

BACKGROUND: Allergic conjunctivitis is commonly observed eye diseases in Sikkim, India due to the abundance of seasonal pollens, environmental pollutants, and house dust. We evaluated the efficacy of topical 0.03% tacrolimus eye ointment in the management of simple allergic conjunctivitis. MATERIALS AND METHODS: A prospective observational study was designed consisting of 41 patients with refractory simple allergic conjunctivitis, whose condition responded very poorly to conventional anti-allergic eye drops (azelastine, olopatadine, chlorpheniramine maleate, sodium chromoglycate). Simple allergic conjunctivitis cases were diagnosed and followed up evaluating both subjective and objective findings (itching, photophobia, tearing, chemosis, conjunctival congestion, tarsal papilla, and eyelid edema). Existing ocular treatment was discontinued at enrolment and 0.03% tacrolimus ointment was applied into the conjunctival sac of the affected eyes twice daily for 4 weeks followed by a 2 weeks washout period. Patients were followed up at the end of 1(st) week, 4(th) week, and at 7(th) week (2 weeks washout period). RESULTS: Symptoms of simple allergic conjunctivitis (itching, tearing and photophobia) were significantly reduced at the end of 1(st) week. Signs such as conjunctival chemosis, congestion, tarsal papillae, and eyelid edema were effectively treated in all cases at the end of 1(st) week. At the end of 4(th) week, all cases were fully cured and none of the patient had any recurrences up to 7(th) week. Mean score at 1(st) day (9.6 ± 3.27) was significantly (P < 0.0001) reduced by 7(th) day (1.35 ± 1.19) of treatment. CONCLUSION: Topical application of tacrolimus ointment is an excellent alternative to anti-allergic and steroids eye drops for the treatment of simple allergic conjunctivitis as it significantly reduces recurrences.

Mycotoxin detection on antibody-immobilized conducting polymer-supported electrochemically polymerized acacia gum.

Electrochemical polymerization of acacia gum (AG) was initiated by electroactive polyaniline (PANI) monomers by radical cation formation and their coupling reactions with AG molecules. R(CT) values obtained from electrochemical impedance spectroscopy analysis at various AG concentrations with PANI were drastically decreased, confirming formation of conducting AG complexes with PANI. Quantitative analysis of ochratoxin-A (OTA) detection in electrolyte was carried out on rabbit antibody-immobilized PANI and PANI-AG matrices. The observed sensitivities of 50, 150, and 250 mg AG-added PANI matrix-based platforms were 3.3 ± 0.5, 10.0 ± 0.5, and 12.7 ± 0.5 µA/ng/ml, respectively. The sensitivity of only PANI electrodes was 2.6 ± 0.3 µA/ng/ml, which was relatively lower than AG-added PANI. This increase was due to the presence of glycan functional groups in AG molecules that supported the retention of activity of antibodies. In addition, enhanced electron transportation at AG-PANI film surface was observed due to formation of an electroactive polymer film of two different electroactive functions to contribute toward enhancement in the detection sensitivity.

The estrogenic effects of Polygonum hydropiper root extract induce follicular recruitment and endometrial hyperplasia in female albino rats.

INTRODUCTION: The powdered dry root of Polygonum hydropiper is widely used by a certain ethnic group of women in Assam, India, for the prevention of undesired pregnancy. METHOD: In the present investigation, the estrogenic property of the crude root extract (CRE) of P. hydropiper [compared to estradiol-17beta (E(2)), the reference drug] was tested in ovary-intact and ovariectomized (OVX) rats. The study was carried out by histological observations of ovarian follicles in an ovary-intact model and by histological observations of the endometrial epithelium in both OVX and ovary-intact female albino rats. Serial sections of the ovary and of the uterus were stained with routine hematoxylin-eosin and were observed under a microscope. RESULTS: In the ovary-intact model, CRE induced follicular recruitment, while it promoted follicular atresia at a later stage. Many of the graafian follicles in the treated ovary showed pyknosis of the nuclei of granulosa and theca cells, as well as disparity in granulosa cell organization. In the uterine tissues of both ovary-intact and OVX rats, CRE induced hyperplasia in places of luminal epithelium and degeneration of endometrial glands. In OVX rats, the effect of CRE on uterine endometrium was corroborative with the effect of E(2). CONCLUSIONS: Oral administration of the CRE of P. hydropiper significantly altered the histological structures of both ovary-intact and OVX rats.

Polygonum hydropiper crude root extract mimics estrogenic properties in females: Evidence of uterine protein profiles studied by sodium dodecyl sulfate polyacrylamide gel electrophoresis.

Polygonum hydropiper is a widely grown weed in the north-eastern states of India. In the present study, estrogenic effects of the crude root extract (CRE) of Polygonum hydropiper on uterine protein was tested in ovary-intact and ovariectomized (OVX) female albino rats. The methanolic crude extract of Polygonum hydropiper was given to adult ovary-intact and OVX female albino rat in a dose of 1000 mg/kg bodyweight per day. Oral administration of the CRE was carried out for a period of 12 days from the onset of proestrus and for a similar period of time for the OVX female. To study the estrogenic effect, OVX females were subcutaneously injected with 0.1 µg of estradiol-17ß (E2). E2 was injected at the interval of 24 h for a total period of 72 h. The uterine protein of ovary-intact and OVX females was studied by single dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis. The results showed similar protein bands in OVX females treated with E2 and CRE. In addition, treatment with CRE stimulated expression of more proteins in the uterus. The results showed that CRE of Polygonum hydropiper mimics the effect of estradiol-17ß in the uterine protein profiles of adult female albino rats. (Reprod Med Biol 2006; 5: 155-160).