The effects of hyaluronic acid vaginal gel on the vaginal epithelium of ovariectomized rats

An experimental model of dryness on vaginal mucosa is proposed to assess the efficacy of a new vaginal gel (Respecta® Hydragel Ref 17031). The dryness model was induced on reconstituted human vaginal epithelium (HVE) by incubating the tissues in modified environmental conditions (R.H. < 50% and T = 40 °C) for 48 h. The products were applied on the ‘Dry’ HVE models for 24 h (series 48 h + 24 h) in standard culture conditions (37 °C 5% CO2). Their efficacy in counteracting vaginal dryness was assessed and compared to tissues treated with saline solution and cultured in standard culture conditions (negative control) and to untreated tissues incubated in dryness conditions for 48 h and then recovered after 24 h in standard culture conditions (positive control). The products’ efficacy was quantified by measuring the following parameters: (1) water flux and direct moisturization by AQP3 immunohistochemical staining, and (2) maintenance of moisturization and elasticity of the mucosa by hyaluronic acid (CD44) immunofluorescence staining. Respecta® Hydragel demonstrated efficacy in regulating the water flux by inducing AQP3 expression thus determining a positive water balance within the vaginal epithelium. It induced a remodelling of the epithelium morphology with restored trophism compared to the dry HVE control. Furthermore, it demonstrated a significant increase of the expression of CD44, related to hyaluronic acid (HA) distribution in the extracellular matrix. HA has the ability to act on the cellular matrix composition and its renewal compared to the dry HVE control. Through these mechanisms it induces a deep hydration and elasticity of the vaginal mucosa.

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THE INVESTIGATION OF PHARMACOLOGICAL PROPERTIES OF VAGINAL GEL WITH RESVERATROL AND HYALURONIC ACID IN CONDITIONS OF EXPERIMENTAL HYPOESTROGENIC STATE IN RATS

Medical Science of Ukraine (MSU) ◽

10.32345/2664-4738.1.2021.10 ◽

2021 ◽

Vol 17 (1) ◽

pp. 74-82

Author(s):

O.A. Stryha ◽

G.V. Zaychenko ◽

S.I. Savosko ◽

K.Y. Sorokopud

Keyword(s):

Hyaluronic Acid ◽

Sex Hormones ◽

Hormone Replacement ◽

Female Rats ◽

Ovariectomized Rats ◽

Blood Levels ◽

Vaginal Mucosa ◽

Pharmacological Properties ◽

Vaginal Gel ◽

Vaginal Secretions

Relevance. The menopausal period due to irreversible loss of ovarian function is accompanied by various clinical symptoms and systemic changes. In turn, hormone replacement therapy has a number of contraindications and side effects, so now there is a need to find and create prophylactic and therapeutic agents based on natural compounds that are related to β-estrogen receptors. Vaginal gel with resveratrol and hyaluronic acid can reduce atrophic manifestations of the vaginal mucosa and affect various symptoms of menopause. However, the nature of the effect, dosage, and consequences of long-term use of resveratrol need further study. Objective: to study pharmacological properties of a new vaginal gel with resveratrol and hyaluronic acid (HA) in a model of hypoestrogenism in ovariectomized rats. Materials and methods. The experiments were performed on 24 outbred white nonlinear female rats, which were divided into 4 groups: intact control, controlled pathology, controlled pathology, and administration of resveratrol with hyaluronic acid, controlled pathology, and administration of a comparison drug with synthetic estrogen. The effectiveness of the drugs was assessed by their effect on the blood levels of the sex hormones estrogen and progesterone, on body weight, on body temperature, on the pH of vaginal secretions, on the state of the vaginal mucosa. Results. 28-day vaginal injection of gel with resveratrol and hyaluronic acid slowed down and normalized weight gain of ovariectomized female rats, stabilized skin temperature and induced normalization of the pH of vaginal secretions of the vagina, normalized the level of sex hormones in the blood, promoted the restoration of the epithelial plate of the vagina. Conclusions. The results showed the feasibility of developing and using a new vaginal gel with resveratrol as an alternative to hormone-containing drugs for the prevention or treatment of pathological hypoestrogenic conditions arising from estrogen deficiency.

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Evaluation of the Efficacy and Safety of Hyaluronic Acid Vaginal Gel to Ease Vaginal Dryness: A Multicenter, Randomized, Controlled, Open‐Label, Parallel‐Group, Clinical Trial

Journal of Sexual Medicine ◽

10.1111/jsm.12125 ◽

2013 ◽

Vol 10 (6) ◽

pp. 1575-1584 ◽

Cited By ~ 60

Author(s):

Junya Chen ◽

Li Geng ◽

Xuehong Song ◽

Hongxia Li ◽

Nicola Giordan ◽

...

Keyword(s):

Clinical Trial ◽

Hyaluronic Acid ◽

Efficacy And Safety ◽

Open Label ◽

Vaginal Dryness ◽

Randomized Controlled ◽

Vaginal Gel ◽

Parallel Group

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DETERMINATION OF THE BIOADHESION INDICATORS OF VAGINAL GEL WITH RESVERATROL AND HYALURONIC ACID

EUREKA Health Sciences ◽

10.21303/2504-5679.2019.00880 ◽

2019 ◽

Vol 2 ◽

pp. 33-39

Author(s):

Olena Ivaniuk ◽

Tatyana Yarnykh ◽

Inna Kovalevska

Keyword(s):

Hyaluronic Acid ◽

Sodium Alginate ◽

Methyl Cellulose ◽

Reference Drug ◽

Vinyl Methyl Ether ◽

Vaginal Gel ◽

Adhesion Ability ◽

Composition Materials ◽

Chemical Studies ◽

Adhesive Ability

Aim. The purpose of the work is to determine the bioadhesion indices of vaginal gel with resveratrol and hyaluronic acid, as well as the choice of the type and content of mucoadhesives in the composition. Materials and methods. As research objects samples of gels with different mucoadhesives in the composition were used. Among used mucoadhesives were: sodium alginate (FMC BioPolimer AS, Norway), methyl cellulose (Shin Etsu, Germany), Methocel – methyl cellulose with hydroxypropylmethyl cellulose (Dow Pharmaceutical Sciences, USA), OraRez® W-100L16 – vinyl methyl ether and maleic anhydride copolymer (BOAI, China). As a comparison drug, vaginal gel "Gynodec" (Yuriya-Pharm) was used. During the study, the rate of gel distribution, the degree of deformation under the influence of mechanical forces, the degree of the gel fixation on the surface of the mucosa and the adhesion ability of the samples have been determined. Results. The study has determined that sample No. 2 with sodium alginate has the highest distribution rate, which was 1.56 cm/min. The study of the fixation of samples on the surface of the model of the mucous was performed by the method of flow. The results have showed that the sample with sodium alginate has the closest value to the reference drug. The adhesive ability of samples with different sodium alginate contents was determined. The tensimetric study has found that at a concentration of 0.5 %, the force required to separate the surface is 6158 Pa. Conclusions. On the basis of the complex of physico-chemical studies, bioadhesion indicators of vaginal gel with resveratrol, depending on the type and concentration of mucoadhesives have been determined. According to the distribution parameters on the surface of the genital mucosa model, it has been found that the best properties compared with other types of mucoadhesives has a sample containing sodium alginate. The study by means of a strain gauge has found that the addition of sodium alginate at a concentration of 0.5 % would provide a satisfactory adhesive ability of the vaginal gel.

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Response of vaginal epithelium and the quantitative estimation of its cellular proliferation in ovariectomized rats after a single administration of oestradiol

Cells Tissues Organs ◽

10.1159/000144159 ◽

1974 ◽

Vol 87 (1) ◽

pp. 82-92

Author(s):

A.K. Sanyal ◽

Shamer Singh ◽

S.P. Singh

Keyword(s):

Cellular Proliferation ◽

Quantitative Estimation ◽

Vaginal Epithelium ◽

Ovariectomized Rats ◽

Single Administration

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Effects of estrogen-like plant compounds on the vaginal epithelium pituitary, adrenal glands, and uterus of rats

Experimental Biology and Medicine ◽

10.1177/1535370218817503 ◽

2018 ◽

Vol 243 (15-16) ◽

pp. 1173-1184

Author(s):

Gismar MC Rodrigues ◽

Bruno DB Borges ◽

Leticia Gabriela Q Moreira ◽

Érica Aparecida G Rossete ◽

Suzelei de Castro Franca

Keyword(s):

Estrogen Receptor ◽

Mechanism Of Action ◽

Adrenal Glands ◽

Estrogenic Activity ◽

Reproductive Organs ◽

Colocasia Esculenta ◽

Vaginal Epithelium ◽

Female Rats ◽

Ovariectomized Rats ◽

Prolonged Treatment

Plant species with recognized estrogenic activity and widely used by Brazil’s female population to prevent the unpleasant symptoms of menopause were investigated in this work to demonstrate if constituents of taro-inhame ( Colocasia esculenta), cumaru ( Dipteryx odorata), and camapu ( Physalis angulata) have the ability to mimic or interfere with the action of estrogens. Moreover, their potential use as natural sources of estrogen-like substances for hormone replacement therapy was evaluated. (a) In vivo pharmacological assays were conducted to determine the estrogenic effects of D. odorata isoflavone-rich extract, P. angulata physalin-rich extract, and C. esculenta flavonoid glycoside-rich fraction (FG) on endocrine glands and reproductive organs of female rats at three different stages of the life cycle. The protocols consisted of uterotrophic assays and cytological evaluation of vaginal smears to detect mucosa cell alterations correlated with changes in hormone levels in each phase of the estrous cycle of female rats. The results indicated that C. esculenta FG exhibited estrogenic activity in prepubescent, pubescent, and adult ovariectomized female rats, while D. odorata isoflavones only promoted a weight increase in the pituitary gland of prepubescent rats after prolonged treatment and P. angulata physalins induced a weight increment in the adrenal glands of ovariectomized rats. Additionally, C. esculenta exerted a significant effect on the opening of the vaginal canal in prepubescent rats and on vaginal epithelium. Prolonged treatment of ovariectomized rats with FG altered the proportion of different types of vaginal epithelial cells in these animals, suggesting an interference of FG with estrogen levels. Colocasia esculenta FG induced hypertrophy of the uterus and pituitary in ovariectomized rats similar to estradiol. To elucidate the mechanism of action of FG, its effects were compared to those of estradiol and of the selective estrogen receptor modulator raloxifene. The results suggest that the efficacy of C. esculenta FG is mediated by binding to selective estrogen receptors present in each organ and that raloxifene inhibits the mechanism of action of FG in the same way as it inhibits the effects of estradiol. The overall findings indicate that C. esculenta FG mimics the action of estrogens, with reduced harmful effects on specific tissues. Impact statement The results of this work provide preliminary evidence that ovariectomized rats display the vaginal smear cells typical of the estrous phase of mature rats after long-term ingestion of Colocasia esculenta flavonoid glycosides. Moreover, the treatment caused beneficial effects on endocrine and reproductive organs compared to estradiol. The animals did not exhibit significant body weight alterations among the groups, demonstrating the maintenance of standard metabolism and energy balance. The overall findings obtained with the rat model of menopause highlight the importance of dietary consumption of C. esculenta constituents as potential selective estrogen receptor modulators and suggest that they may prevent some of the metabolic disorders related to estrogen deficiency.

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