Date (Phoenix dactylifera L. Mill) fruit enhances sexual performance via modulation of oxido-inflammatory mediators and purinergic signaling in hypertensive male rats.

INTRODUCTION: The present study aimed at investigating the effect of dietary supplementation of Phoenix dactylifera, an important component of aphrodisiac supplements, on sexual performance, oxido-inflammatory mediators and purinergic signaling system in hypertensive rats. MATERIAL AND METHODS: Hypertension was induced via oral administration of 40 mg/kg L-NAME. Thereafter, the sexual performance of the experimental animals was determined and the hypertensive rats with impaired sexual activities were placed on P. dactylifera-supplemented diet for 21 days, and the effects of the treatment on the overall sexual behavior, antioxidant status, oxido-inflammatory biomarkers, and enzyme activity of the purinergic system were assessed. RESULTS: Hypertensive rats showed a significant (p < 0.05) decrease in sexual performance, elevated level of oxido-inflammatory mediators, and altered purinergic enzymes activity when compared with the control. However, sub-chronic feeding with P. dactylifera-supplemented diet improved sexual performance, significantly lowered oxido-inflammatory biomarkers, and enhanced the activity of purinergic enzymes in hypertensive rats. CONCLUSION: Findings presented in this study suggest that dietary inclusion of P. dactylifera could be useful in managing erectile dysfunction (ED) commonly observed in subjects with hypertension. Findings highlighted in this study thus provide the scientific basis supporting the folkloric use of P. dactylifera as a key ingredient in aphrodisiac supplements.

A comprehensive review of Pfaffia glomerata botany, ethnopharmacology, phytochemistry, biological activities, and biotechnology.

ETHNOPHARMACOLOGICAL RELEVANCE: Pfaffia glomerata (Spreng.) Pedersen, Amaranthaceae, is found in South America, mainly in Brazil, where it is considered a species of great medicinal interest owing to its popular use as a tonic, aphrodisiac, anti-inflammatory, and analgesic. These properties can be attributed to the presence of the phytosteroid, 20-Hydroxyecdysone (ß-ecdysone), the main compound found in its roots. AIM OF THE REVIEW: This review aims to provide information about the botanical characteristics, ethnomedicinal uses, the phytochemistry, the biological activities, and the biotechnology of P. glomerata, an important species to local communities and groups researching medicinal plants of South America. MATERIALS AND METHODS: The information available on P. glomerata was collected from scientific databases (ScienceDirect, PubMed/MEDLINE, SciELO, and Scopus) until June 7, 2023, using the search terms "Pfaffia glomerata", "Pfaffia glomerata (Spreng.) Pedersen", and "Brazilian ginseng". The review includes studies that evaluated the botanical, ethnopharmacological, and phytochemical aspects, biological properties, nutraceutical uses, and the application of biotechnology for improving the biosynthesis of metabolites of interest. RESULTS: A total of 207 studies were identified, with 81 articles read in full. Seventy-six studies were included for qualitative synthesis. Overall, 40 compounds belonging to different classes are presented in this review, including ecdysteroids, triterpenes, saponins, flavonoids, anthraquinones, tannins, coumarins, alkaloids, and polysaccharides. Among them, flavonoids, anthraquinones, tannins, coumarins, and alkaloids were only putatively identified. ß-Ecdysone, triterpenes, saponins, and polysaccharides are the chemical components most frequently identified and isolated from P. glomerata and possibly responsible for ethnopharmacological use and the biological activities of this species, with important in vitro and in vivo activities, such as anti-inflammatory, antidepressant, aphrodisiac, analgesic, gastroprotective, antioxidant, and prebiotic. CONCLUSIONS: This review summarizes discussions about the P. glomerata species, highlighting its ethnopharmacological, chemical, biotechnological, and nutraceutical importance. New scientific studies on this species are encouraged in the search for new therapeutic molecules with pharmaceutical potential and nutraceutical applications.

A multi-modal approach to investigate Desmodium gangeticum's influence on stress-induced male infertility: In vivo, in vitro, and in silico assessments.

Physical and psychological stress has an inverse relation with male libido and sperm quality. The present study investigates the potential fertility-enhancing properties of Desmodium gangeticum (DG) root extracts in male Wister rats subjected to immobilization-induced stress (SIMB). DG roots were extracted using n-hexane (HEDG), chloroform (CEDG), and water (AEDG). In the pilot study, aphrodisiac protentional was investigated at two doses (125 and 250 mg kg-1) of each extract. In the main study, the HEDG and AEDG at 125 and 250 mg kg-1 were challenged for the stress by immobilization (SIMB), for 6 h daily over 28 days. Parameters assessed included aphrodisiac effects, gonadosomatic index (GSI), semen quality, sperm quantity, fructose content, serum hormonal levels, testicular oxidative stress, and testicular histopathology. Additional in silico studies, including the lipid solubility index, molecular docking, molecular dynamics, and SymMap studies were conducted for validation. HEDG demonstrated significant aphrodisiac activity, improved - GSI, sperm quality and quantity, and fructose content, serum testosterone levels, histological changes induced by SIMB in the testes. Swiss ADME studies indicated Gangetin (a pterocarpan) had a high brain permeation index (4.81), a superior docking score (-8.22), and higher glide energy (-42.60), compared with tadalafil (-7.17). The 'Lig fit Prot' plot in molecular dynamics simulations revealed a strong alignment between Gangetin and phosphodiesterase type 5 (PDE5). HEDG exerts aphrodisiac effects by increasing blood testosterone levels and affecting PDE5 activity. The protective effects on spermatozoa-related parameters and testicular histological changes are attributed to the antioxidant and anti-inflammatory properties, of pterocarpan (gangetin).

Saffron (Crocus sativus L.) extract attenuates chronic scopolamine-induced cognitive impairment, amyloid beta, and neurofibrillary tangles accumulation in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Crocus sativus L. known as saffron, is a popular food condiment with a high aroma, deep colour, and long and thick threads (stigmas) cultivated in Iran, Morocco, Spain, Italy, China, Japan, France, Turkey, and India. In 'Ayurveda', saffron is acknowledged for its immunostimulant, aphrodisiac, cardiotonic, liver tonic, nervine tonic, carminative, diaphoretic, diuretic, emmenagogue, galactagogue, febrifuge, sedative, relaxant, and anxiolytic activities. The renowned Persian physician and philosopher, Avicenna, delineated saffron as an antidepressant, hypnotic, anti-inflammatory, hepatoprotective, bronchodilator, and aphrodisiac in his book, the Canon of Medicine. Within traditional Iranian Medicine (TIM), saffron is characterized as a mood elevator and a rejuvenator for the body and senses. Further, the ethnopharmacological evidence indicates that saffron has shown an effect against neurodegenerative disorders namely, dementia, Alzheimer's, and Parkinson's with its bioactive constituents i.e., carotenoids and apocarotenoids. AIM: The present study aimed to investigate the potential of standardized (Kashmir Saffron, India) Crocus sativus extract (CSE) in chronic scopolamine-induced cognitive impairment, amyloid beta (Aß) plaque, and neurofibrillary tangles (NFT) accumulation in rat brains by targeting AChE inhibition and scopolamine mechanistic effect. METHODS: The experimental animals were divided into six groups: group 1: normal control, group 2: scopolamine, group 3,4 and 5 rivastigmine tartrate, CSE (p.o. 10 mg/kg, 15 mg/kg, and 20 mg/kg) respectively. Each treatment group received scopolamine after 20 min of dosing, till 4 weeks. The effects of different treatments on learning, acquisition, and reversal memory were performed using a Morris water maze test. In addition to behavioral assessments, biochemical parameters such as AChE, IL-6, and antioxidants were measured in isolated brains. Histological observations were also conducted to assess the presence of Aß plaques and NFT. Furthermore, molecular docking was performed to explore the potential AChE inhibitory activity of the bioactive constituents of standardized CSE. RESULTS: Scopolamine produces memory impairment, and its chronic administration forms Aß plaque and NFT in rat brains. Supplementation with CSE in presence of scopolamine has shown remarkable effects on behavioural activity, special acquisition, and reversal memory. The CSE has also shown promising effects on AChE inhibition and antioxidant activity. The results of the docking study also indicate that trans-crocetin, i.e., a biologically active metabolite of Crocins, has strong AChE inhibitory activity, supported by an in vivo animal experiment. CONCLUSION: Supplementation with CSE significantly attenuates the formation of Aß plaque and NFT in the hippocampus at a dose of 20 mg/kg per day. In addition, CSE also counters scopolamine-induced neuroinflammation.

UPLC-Q-TOF-MS profiling of Viola stocksii Boiss. and evaluation of aphrodisiac potential and risk factors associated with erectile dysfunction.

ETHNOPHARMACOLOGICAL RELEVANCE: Viola stocksii Boiss. locally known as makhni or makhanr booti, is an important medicinal food plant with multiple therapeutic applications, including erectile dysfunction (ED). It is mixed with butter and used for boosting energy and sexual health in the subcontinent. AIMS OF THE STUDY: This study was designed to evaluate the chemical composition, aphrodisiac potential and effect of V. stocksii on the risk factors associated with ED. METHODOLOGY: The hydroethanolic extract of V. stocksii (HEEVS) was prepared through the microwave-assisted extraction (MAE) technique. The chemical composition was evaluated using preliminary phytochemical screening and UPLC-Q-TOF-MS analysis. Metals and minerals analysis was performed by an atomic absorption spectrophotometer. The aphrodisiac activity of HEEVS was evaluated using an in vivo aphrodisiac model established in male albino rats and the effect on various sexual parameters such as mount, intromission, ejaculation frequencies and mount, intromission, ejaculation latencies, postejaculatory interval, penile reflexes and serum hormone concentration were analyzed. The effect of HEEVS on various risk factors associated with ED, including prostate cancer (PC), bacterial infections, diabetes and obesity, was evaluated using various in vitro assays. Moreover, four compounds were selected from the UPLC-Q-TOF-MS profile and evaluated for in silico computational analysis against phosphodiesterase-5 (PDE-5) for possible interaction. FINDINGS: The phytochemical screening revealed the presence of various secondary metabolites in HEEVS, while 58 compounds were tentatively identified in the UPLC-Q-TOF-MS analysis. Various important minerals and metals such as zinc, calcium, cadmium and magnesium were detected in the atomic absorption spectrometry analysis. The in vivo aphrodisiac evaluation showed a significant (p < 0.05) increase in the mount, intromission and ejaculation frequencies and a decrease in the mount, intromission latencies and post-ejaculatory intervals at a dose of 300 mg/kg. A marked (p < 0.05) increase was observed in the concentration of serum testosterone and luteinizing hormones in HEEVS treated animals with a significant increase in total penile reflexes. The extract displayed significant anti-prostate cancer activity and a potential antibacterial spectrum against E. coli and S. aureus, with MIC50 values of 215.72 µg/mL and 139.05 µg/mL, respectively. Similarly, HEEVS was found active towards pancreatic lipase (67.34 ± 1.03%), α-glucosidase (3.87 ± 0.54 mmol ACAE/g d.w.) and α-amylase (6.98 ± 1.63 mmol ACAE/g d.w.). The in silico docking study presented a potential interaction between the selected compounds and residues of the active site of PDE-5. CONCLUSION: This report highlights the aphrodisiac potential of V. stocksii and provides experimental support for its traditional use in ED with an attenuative effect on the risk factors associated with ED. Moreover, the chemical composition displayed the presence of functional phytoconstituents and minerals in HEEVS and paves the way for the isolation of compounds with potent aphrodisiac activity.

Antihyperglycemic and aphrodisiac effect of West African Albizia (Albizia zygia) leaves-inclusive diet in diabetes-induced erectile dysfunctional rats.

ETHNOPHARMACOLOGICAL RELEVANCE: West African Albizia (Albizia zygia DC J. F. Macbr) leaves are a tropical plant that are frequently used in folkloric medicine to treat a number of illnesses, including type 2 diabetes (TY2D) and erectile dysfunction (ED), without having a complete scientific foundation. AIM OF THE STUDY: This investigation examined the effect of action of dietary augmentation of Albizia zygia leaves (AZL) on rat sexual functioning and important enzymes related to TY2D and ED. MATERIALS AND METHODS: Thirty matured adult Wistar rats of the weight 180-200 g were acclimatized in a lab environmental condition for two weeks prior to experiment given food and water to acclimate. Twenty-four of the rats got high fat diet (HFD) for periods of two weeks before receiving streptozotocin (STZ) intraperitoneally (i.p.), 35 mg/kg body weight single dose. Six rats got basal diets. Type 2 diabetes was identified in rats 72 h after STZ treatment. Rats were then used to evaluate the mounting number, mount delay, intromission number, and intromission latency. RESULTS: Following that, meals supplemented with AZL (5% or 10% inclusion) were given to diabetic-ED rats for 14 days. AZL was added. Therefore, in diabetic-ED rats, AZL supplementation could significantly (p0.05) lower blood glucose levels and the activities of alpha amylase, alpha glucosidase, phosphodiesterase-5, and arginase. In the case of diabetic-ED treated rats in consideration with diabetic-ED control group, nitric oxide levels were increased along with sexual function. CONCLUSION: Thus, experimental results of this study demonstrated rats that consumed AZL in their diets had less erectile dysfunction. In order to address ED caused by diabetes, AZL could be suggested as functional meals.

Female semiochemicals stimulate male courtship but dampen female sexual receptivity.

Chemical communication plays a vital role in mate attraction and discrimination among many insect species. Here, we document a unique example of semiochemical parsimony, where four chemicals act as both aphrodisiacs and anti-aphrodisiacs in different contexts in Bactrocera dorsalis. Specifically, we identified four female-specific semiochemicals, ethyl laurate, ethyl myristate, ethyl cis-9-hexadecenoate, and ethyl palmitate, which serve as aphrodisiacs to attract male flies and arouse male courtship. Interestingly, these semiochemicals, when sexually transferred to males during mating, can function as anti-aphrodisiacs, inhibiting the receptivity of subsequent female mates. We further showed that the expression of elongase11, a key enzyme involved in the biosynthesis of these semiochemicals, is under the control of doublesex, facilitating the exclusive biosynthesis of these four semiochemicals in females and guaranteeing effective chemical communication. The dual roles of these semiochemicals not only ensure the attractiveness of mature females but also provide a simple yet reliable mechanism for female mate discrimination. These findings provide insights into chemical communication in B. dorsalis and add elements for the design of pest control programs.

Evaluating the Aphrodisiac Potential of Mirabilis jalapa L. Root Extract: Phytochemical Profiling and In Silico, In Vitro, and In Vivo Assessments in Normal Male Rats.

The traditional use of Mirabilis jalapa L. roots to enhance male sexual performance prompted us to assess the in silico, in vitro, and in vivo aphrodisiac activities of its hydroethanolic extract using normal male rats. Spectroscopic characterization indicated the presence of ß-D-glucopyranoside, methyl-1,9-benzyl-2,6-dichloro-9H-purine, and Bis-(2-ethylhexyl)-phthalate; these compounds have a significant inhibitory effect on the phosphodiesterase-5 (PDE-5) enzyme in silico evaluation and minerals (including zinc, cadmium, and magnesium). Other phytochemical analyses revealed the presence of phenolic compounds and flavonoids. These phytochemicals and minerals may contribute to the aphrodisiac activities of the extract. Additionally, the in vivo study revealed that the administration of M. jalapa root extract (300 mg/kg) significantly enhanced (p < 0.01, p < 0.03) mount, intromission, and ejaculation frequencies while significantly (p < 0.05) decreasing the mount and intromission latencies, as well as the post-ejaculatory interval time, in comparison with the standard drugs sildenafil and ginseng, resulting in enhanced erection and sexual performance in the rats. Furthermore, the extract significantly (p < 0.05) increased penile reflexes and also elevated the levels of testosterone and luteinizing hormones. Extract (300 mg/kg) significantly (p < 0.05) inhibited the PDE-5 enzyme in an in vitro study. Concludingly, the comprehensive findings of this study suggest that a standardized herbal extract derived from M. jalapa roots alleviates erectile dysfunction and premature ejaculation in male rats. M. jalapa root extract proved to be an alternative treatment for erectile dysfunction and premature ejaculation.

Eco-Friendly UV-Spectrophotometric Methods Employing Magnetic Nano-Composite Polymer for the Extraction and Analysis of Sexual Boosters in Adulterated Food Products: Application of Computer-Aided Design.

BACKGROUND: Solid phase extraction (SPE) techniques, based on computationally designed magnetic-based multi-targeting molecular imprinted polymer (MT-MIP), combined with UV spectrophotometric approaches provide advantages in the examination of counterfeit samples. OBJECTIVE: The current work describes an innovative and sustainable methodology for the simultaneous determination of tadalafil (TAD) and dapoxetine hydrochloride (DAP) in aphrodisiac counterfeit products (honey and instant coffee) utilizing SPE exploiting MT-MIP. Additionally, an innovative UV spectrophotometric method capable of resolving TAD in its pharmaceutical binary mixtures with DAP was developed. A novel computational approach was implemented to tailor the synthesis and design of the MT-MIP particles. METHODS: We applied a newly developed UV spectrophotometric method which was based on a Fourier self-deconvolution (FSD) method coupled with the isoabsorptive point for determination of TAD and DAP in pharmaceutical dosage form. We also applied an SPE process based on MT-MIP designed particles, assisting in the analysis of both drugs in counterfeit food samples. The SPE process and the UV spectroscopic methodology were assessed regarding their greenness using the pioneering green analytical procedure index (GAPI), analytical greeness including sample preparation (AGREEprep) and AGREE tools. The synthesized MT-MIP particles were characterized by scanning electron microscopy and energy-dispersive x-ray spectroscopy. RESULTS: The suggested spectrophotometric methods revealed a wide linear concentration range of 2-50 µg/mL with lower LODs in the range of 0.604-0.994 µg/mL. Additionally, the suggested method demonstrated the utmost sensitivity and eco-friendliness for their target in its mixed dosage form and counterfeit food products. CONCLUSION: The SPE process and the developed analytical UV spectroscopic methodology were validated as per the ICH guidelines, and were found to be suitable for overseeing some counterfeiting activities in commercially available honey and instant coffee aphrodisiac products. HIGHLIGHTS: An SPE method based on MT-MIP magnetic-based polymer and a UV spectroscopic method were successfully developed for analysis of TAD and DAP in different matrices.

Ethnological validation of Ashwagandha (Withania somnifera L. Dunal) ghrita as 'Vajikarana Rasayana': In-silico, in-vitro and in-vivoapproach.

ETHNOPHARMACOLOGICAL RELEVANCE: Processing cow ghee (clarified butterfat) with therapeutic herbs, i.e. ghrita, is recognized for augmenting the therapeutic efficacy of plant materials. Ashwagandha ghrita (AG) is an effective Ayurvedic formulation consisting of Indian ginseng, i.e., Withania somnifera (L.) Dunal, the main constituent used to treat infertility, weakness, gynaecological disorders, and general debility. OBJECTIVES: The present investigation was undertaken to corroborate the ethnopharmacological claim of AG as 'Vajikarana Rasayana' for its aphrodisiac potential using bioinformatics (in-silico) and experimental (in-vitro and in-vivo) approaches. METHODS: AG was formulated as per the methods reported in Ayurved sarsangraha. AG was further subjected to HPLC, GCMS analysis, and biological (acute toxicity and aphrodisiac) assessment per the standard procedures. Thirty-eight bioactives of Indian ginseng were subjected to computational studies (molecular docking and network pharmacology) to confirm the plausible mechanism. RESULTS: AG was found to be safe up to 2000 mg/kg body wt., and it showed dose-dependent upsurge (p < 0.01 and p < 0.05, wherever necessary) in mount and intromission frequency, genital grooming, and anogenital sniffing at 150 and 300 mg/kg body weight suggesting aphrodisiac activity. In-vitro studies demonstrated significant relaxation of the Corpus Cavernosal Smooth Muscle at all concentrations in a dose-dependent manner. Furthermore, the results of molecular modelling studies were in agreement with the biological activity and showed interaction with phosphodiesterase-5 as a possible target. CONCLUSION: AG exhibited an aphrodisiac effect and substantiated the traditional claim of Indian ginseng-based ghrita formulation as 'Vajikarana Rasayana'.

Attitude of literate married men towards the use of aphrodisiac herbs in Ilorin, Kwara state, Nigeria.

Background: Sexual dysfunction among men is on the increase in Nigerian societies; however, many do not seek health care; and may prefer using aphrodisiac herbs. Objectives: We investigated the attitude of literate married men towards the use of aphrodisiac herbs in Ilorin, Kwara State, Nigeria. We also examined whether there would be a significant difference in the attitude of literate married men towards the use of aphrodisiac herbs based on age and educational attainment. Methods: Descriptive survey method was adopted for the study. A total of 200 literate married men were selected through simple random and purposive sampling. The participants responded to a researcher-designed questionnaire. The data were analysed using descriptive and inferential statistics at 0.05 alpha level. Results: The attitude of literate married men was positive. There were significant differences in the attitude of literate married men towards the use of aphrodisiac herbs in Ilorin, Kwara State based on age and educational attainment. Conclusions: Most literate married men in Ilorin, Kwara State, Nigeria had a positive attitude towards the use of aphrodisiac herbs. Doctors and counsellors should organise community-based talk to orientate literate married men on the use of aphrodisiac herbs.

A literature perspective on the pharmacological applications of yohimbine.

Introduction: Phytochemicals have garnered much attention because they are useful in managing several human diseases. Yohimbine is one such phytochemical with significant pharmacological potential and could be exploited for research by medicinal chemists. It is an indole alkaloid obtained from various natural/synthetic sources.Aims and Results: The research on yohimbine started early, and its use as a stimulant and aphrodisiac by humans has been reported for a long time. The pharmacological activity of yohimbine is mediated by the combined action of the central and peripheral nervous systems. It selectively blocks the pre and postsynaptic α2-adrenergic receptors and has a moderate affinity for α1 and α2 subtypes. Yohimbine also binds to other behaviourally relevant monoaminergic receptors in the following order: α-2 NE > 5HT-1A>, 5HT-1B > 1-D > D3 > D2 receptors.Conclusion: The current review highlights some significant findings that contribute to developing yohimbine-based drugs. It also highlights the therapeutic potential of yohimbine against selected human diseases. However, further research is recommended on the pharmacokinetics, molecular mechanisms, and drug safety requirements using well-designed randomized clinical trials to produce yohimbine as a pharmaceutical agent for human use.Key MessagesYohimbine is a natural indole alkaloid with significant pharmacological potential.Humans have used it as a stimulant and aphrodisiac from a relatively early time.It blocks the pre- and postsynaptic α2-adrenergic receptors that could be exploited for managing erectile dysfunction, myocardial dysfunction, inflammatory disorders, and cancer.

Global patterns of illegal marine turtle exploitation.

Human exploitation of wildlife for food, medicine, curios, aphrodisiacs, and spiritual artifacts represents a mounting 21st-century conservation challenge. Here, we provide the first global assessment of illegal marine turtle exploitation across multiple spatial scales (i.e., Regional Management Units [RMUs] and countries) by collating data from peer-reviewed studies, grey literature, archived media reports, and online questionnaires of in-country experts spanning the past three decades. Based on available information, we estimate that over 1.1 million marine turtles were exploited between 1990 and 2020 against existing laws prohibiting their use in 65 countries or territories and in 44 of the world's 58 marine turtle RMUs, with over 44,000 turtles exploited annually over the past decade. Exploitation across the 30-year period primarily consisted of green (56%) and hawksbill (39%) turtles when identified by species, with hawksbills (67%) and greens (81%) comprising the majority of turtles exploited in the 1990s and 2000s, respectively, and both species accounting for similar levels of exploitation in the 2010s. Although there were no clear overarching trends in the magnitude or spatial patterns of exploitation across the three decades, there was a 28% decrease in reported exploitation from the 2000s to the 2010s. The 10 RMUs with the highest exploitation in the 2010s included seven green and three hawksbill turtle RMUs, with most reported exploitation occurring in RMUs that typically exhibit a low risk of population decline or loss of genetic diversity. Over the past decade, the number of RMUs with "moderate" or "high" exploitation impact scores decreased. Our assessment suggests that illegal exploitation appears to have declined over the past decade and, with some exceptions, is primarily occurring in large, stable, and genetically diverse marine turtle populations.

Quassinoids from Eurycoma longifolia and their bone formation evaluation in zebrafish, C3H10 cells and silico.

Phytochemicals with bone formation potential in traditional medicines captured more and more attentions due to their advantages to bone loss and fewer side effects. As a famous aphrodisiac phytomedicine, Eurycoma longifolia (EL) has acquired general recognition in improving male sexual health, and thus been considered as traditional medicine for the treatment of androgen-deficient osteoporosis. Although the aqueous extract of EL had been proved to be beneficial to bone loss, the active constituents and the mechanisms underlying the effects are still obscure. The current study performed a chemical investigation on the roots of EL, which resulted in the isolation and identification of ten quassinoids (EL-1-EL-10), and then conducted their osteogenic activity evaluations in vivo zebrafish model with or without dexamethasone (Dex) and in vitro C3H10 cell model. The result displayed that most tested concentrations of EL-1-EL-5 could significantly increase the mineralization areas and integrated optical densities (IODs) of skull in both zebrafish model. The majority tested concentrations of EL-1-EL-5 could also improve the mRNA expression of early osteogenic associated genes ALPL, Runx2a, Sp7 in zebrafish model without Dex, but only a few could accelerate the mRNA expression of late osteogenic associated genes OCN. These results suggested the ability of EL-1-EL-5 to increase bone formation mainly by accelerating osteogenic differentiation at the early stage. The structure-based virtual screening based on the pharmacophores in ePharmaLib, as well as the molecular docking study, implied that the effects of the quassinoids (EL-1-EL-5) on the enhancement of bone formation might be related with improving the content and the activity of androgen through binding with CYP19A, SHBG and AKR1C2, and activating bone metabolism-related ANDR target genes and signal pathways by combining with ANDR directly. Although the assumptions are in silico model-based and further in vitro and in vivo validations are still necessary, we provided a new perspective to explore the potential of EL to be used as an alternative treatment for not only androgen-deficient osteoporosis, but also estrogen-deficient bone loss, by combining with SHBG.

Anticancer potential of yohimbine in drug-resistant oral cancer KB-ChR-8-5 cells.

BACKGROUND: The demand for environmentally friendly and cost-effective plant-based products for the development of cancer therapeutics has been increasing. Yohimbine (α2-adrenergic receptor antagonist) is a stimulant and aphrodisiac used to improve erectile dysfunction. In this study, we aimed to evaluate the anticancer potential of yohimbine in drug-resistant oral cancer KB-ChR-8-5 cells using different biomolecular techniques. METHODS: We estimated the anticancer efficacy of yohimbine using different assays, such as MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) cell cytotoxicity, cell morphology, cell apoptosis, reactive oxygen species (ROS) formation, and modulation in the mitochondrial membrane potential (MMP). RESULTS: Yohimbine showed a dose-dependent increase in cytotoxicity with a 50% inhibitory concentration (IC50) of 44 µM against KB-ChR-8-5 cancer cell lines. Yohimbine treatment at 40 µM and 50 µM resulted in a considerable change in cell morphology, including shrinkage, detachment, membrane blebbing, and deformed shape. Moreover, at the dose of IC50 and above, a significant induction was observed in the generation of ROS and depolarization of MMP. The possible mechanisms of action of yohimbine underlying the dose-dependent increase in cytotoxicity may be due to the induction of apoptosis, ROS generation, and modulation of MMP. CONCLUSION: Overall, yohimbine showed a significant anticancer potential against drug-resistant oral cancer KB-ChR-8-5 cells. Our study suggests that besides being an aphrodisiac, yohimbine can be used as a drug repurposing agent. However, more research is required in different in vitro and in vivo models to confirm the feasibility of yohimbine in clinics.

Crocin molecular signaling pathways at a glance: A comprehensive review.

Crocin is a hydrophilic carotenoid that is synthesized in the flowers of the Crocus genus. Numerous in vitro and in vivo research projects have been published about the biological and pharmacological properties and toxicity of crocin. Crocin acts as a memory enhancer, anxiolytic, aphrodisiac, antidepressant, neuroprotective, and so on. Here, we introduce an updated and comprehensive review of crocin molecular mechanisms based on previously examined and mentioned in the literature. Different studies confirmed the significant effect of crocin to control pathological conditions, including oxidative stress, inflammation, metabolic disorders, neurodegenerative disorders, and cancer. The neuroprotective effect of crocin could be related to the activation of phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT)/mammalian target of rapamycin (mTOR), Notch, and cyclic-AMP response element-binding protein signaling pathways. The crocin also protects the cardiovascular system through the inhibitory effect on toll-like receptors. The regulatory effect of crocin on PI3K/AKT/mTOR, AMP-activated protein kinase, mitogen-activated protein kinases (MAPK), and peroxisome proliferator-activated receptor pathways can play an effective role in the treatment of metabolic disorders. The crocin has anticancer activity through the PI3K/AKT/mTOR, MAPK, vascular endothelial growth factor, Wnt/ß-catenin, and Janus kinases-signal transducer and activator of transcription suppression. Also, the nuclear factor-erythroid factor 2-related factor 2 and p53 signaling pathway activation may be effective in the anticancer effect of crocin. Finally, among signaling pathways regulated by crocin, the most important ones seem to be those related to the regulatory effect on the PI3K/AKT/mTOR pathway.

The aphrodisiac potential of ß-cyclodextrin-curcumin via stimulating cAMP-PKA pathway in testicular Leydig cells.

The water-soluble ß-cyclodextrin-curcumin (CDC) is used in pharmaceutical applications and as a natural food colorant. The previous study revealed that curcumin potentially impacted the reproductive system. The present study investigated the possible roles of the CDC in testosterone secretion in Leydig cells and mice. Primary Leydig cells were treated with the CDC to determine their effect on cell proliferation, testosterone levels, the protein and mRNA expression of the transcription factor, and steroidogenic enzymes. Our data showed that CDC stimulated testosterone production via upregulating transcription factor steroidogenic factor-1 (NR5A1), cAMP-response element-binding protein (CREB), and steroidogenic enzymes steroidogenic acute regulatory protein (StAR), cholesterol side-chain cleavage enzyme (CYP11A1), 17-alpha-hydroxylase/17,20-lyase (CYP17A1), 3ß-/17ß-hydroxysteroid dehydrogenase type 1 (3ß/17ß-HSD, HSD3b1/HSD17b1). CDC could significantly stimulate H89-suppressed StAR and CREB expression but not reverse melatonin-suppressed StAR expression. We further detected the hormonal activity with transgenic yeast, and CDC showed potential androgenic antagonistic activity. Meanwhile, we investigated its aphrodisiac effect on hydrocortisone-induced mice. Exposure to hydrocortisone decreased the mating ability, reproductive organs, and testosterone level and disrupted testicular histology. However, all of these effects were significantly improved by CDC treatment. In conclusion, these results indicated that mechanisms of CDC in stimulating testosterone production involve upregulating the cAMP-PKA pathway.

Eugenol reduces serum testosterone levels and sperm viability in adult Wistar rats.

Eugenol is the main constituent of clove extract. It is a remarkably versatile molecule incorporated as a functional ingredient in several food products and widely applied in the pharmaceutical industry. Men consume natural products enriched with eugenol for treating sexual disorders and using as aphrodisiacs. Nevertheless, there is no information about the impact of eugenol intake on the reproductive parameters of healthy males. Therefore, we provided 10, 20, and 40 mg kg-1 pure eugenol to adult Wistar rats for 60 days. Testis, epididymis, and spermatozoa were analyzed under microscopic, biochemical, and functional approaches. This phenolic compound did not alter testicular and epididymal biometry and microscopy. However, 20 and 40 mg kg-1 eugenol reduced serum testosterone levels. The highest dose altered lactate and glucose concentrations in the epididymis. All the eugenol concentrations diminished CAT activity and MDA levels in the testis and increased FRAP and CAT activity in the epididymis. Epididymal sperm from rats receiving 10, 20, and 40 mg kg-1 eugenol presented high Ca2+ ATPase activity and low motility. In conclusion, eugenol at low and high doses negatively impacted the competence of epididymal sperm and modified oxidative parameters in male organs, with no influence on their microscopy.

Aphrodisiac Performance of Bioactive Compounds from Mimosa pudica Linn.: In Silico Molecular Docking and Dynamics Simulation Approach.

Plants and their derived molecules have been traditionally used to manage numerous pathological complications, including male erectile dysfunction (ED). Mimosa pudica Linn. commonly referred to as the touch-me-not plant, and its extract are important sources of new lead molecules in drug discovery research. The main goal of this study was to predict highly effective molecules from M. pudica Linn. for reaching and maintaining penile erection before and during sexual intercourse through in silico molecular docking and dynamics simulation tools. A total of 28 bioactive molecules were identified from this target plant through public repositories, and their chemical structures were drawn using Chemsketch software. Graph theoretical network principles were applied to identify the ideal target (phosphodiesterase type 5) and rebuild the network to visualize the responsible signaling genes, proteins, and enzymes. The 28 identified bioactive molecules were docked against the phosphodiesterase type 5 (PDE5) enzyme and compared with the standard PDE5 inhibitor (sildenafil). Pharmacokinetics (ADME), toxicity, and several physicochemical properties of bioactive molecules were assessed to confirm their drug-likeness property. Molecular dynamics (MD) simulation modeling was performed to investigate the stability of PDE5-ligand complexes. Four bioactive molecules (Bufadienolide (-12.30 kcal mol-1), Stigmasterol (-11.40 kcal mol-1), Isovitexin (-11.20 kcal mol-1), and Apigetrin (-11.20 kcal mol-1)) showed the top binding affinities with the PDE5 enzyme, much more powerful than the standard PDE5 inhibitor (-9.80 kcal mol-1). The four top binding bioactive molecules were further validated for a stable binding affinity with the PDE5 enzyme and conformation during the MD simulation period as compared to the apoprotein and standard PDE5 inhibitor complexes. Further, the four top binding bioactive molecules demonstrated significant drug-likeness characteristics with lower toxicity profiles. According to the findings, the four top binding molecules may be used as potent and safe PDE5 inhibitors and could potentially be used in the treatment of ED.

A Social-Ecological Study of Perceptions and Determinants of Sexual Enhancement Drug Use among Men and Women in Ghana.

The use and sale of sexual enhancement drugs (particularly unapproved aphrodisiacs) have become a public health concern in Ghana and many other sub-Saharan African countries. While most studies have examined this phenomenon from the level of individual perspectives, this study investigates the multi-dimensional and multi-level factors (e.g., individual characteristics and behaviours, interpersonal factors, community norms and practices, institutional and public policy factors) that influence attitudes, perceptions, and use of aphrodisiacs among men and women in Ghana. Using a concurrent mixed-method design, we derived the data from a semi-structured interview and cross-sectional survey conducted across five administrative regions in Ghana. Interpretative phenomenological analysis and logistic regression techniques were used to analyse the qualitative and quantitative (survey) data, respectively. Approximately 12.6% of participants (17.6% among males and 7.2% among females) had used an aphrodisiac in the six months prior to the study. Approximately 23.4% of the participants had more than one partner during the same period. Among men, being religious (B = −0.238, p < 0.05) and having multiple sexual partners (B = 0.481, p < 0.01) were positively associated with the use of aphrodisiacs. For women, being employed (B = −1.539, p < 0.01), engaging in physical activities (exercising) (B = −0.658, p < 0.05), having good health (B = 0.869, p < 0.05), having multiple sexual partners (B = 1.191, p < 0.01), and taking alcohol (B = 1.041, p < 0.01) were associated with use of aphrodisiacs. Although many participants had used aphrodisiacs, women, in particular, held unfavourable views about the drugs due to perceived negative health implications for themselves and their partners. The findings also show that community-level factors (e.g., social norms and expectations), interpersonal factors (e.g., expectations of partners and friends), public policy (e.g., drug-related regulations), and organisational/institutional factors (e.g., health system arrangements about access and use of drugs) were critical to the sale and use of aphrodisiacs among both men and women in Ghana. A multi-level analysis of the use of sexual enhancement drugs among men and women is crucial to formulating social and public health policies that aim to improve public knowledge of these drugs, reduce uncontrolled production, and protect population health and well-being.