5α-reductase Activity Research Articles

Hair Growth-Promoting Effect of Hydrangea serrata (Thunb.) Ser. Extract and Its Active Component Hydrangenol: In Vitro and In Vivo Study.

With the escalating prevalence of hair loss, the demand for effective hair loss treatment has surged. This study evaluated the effects of hot water extract of Hydrangea serrata (Thunb.) Ser. leaf (WHS) on hair growth, employing cell cultures, mice, and human skin organoid models. Both WHS and hydrangenol were found to enhance 5α-reductase inhibitory activity. WHS and hydrangenol have been shown to stimulate dermal papilla cell (DPC) growth, potentially through factors like keratinocyte growth factor (KGF), fibroblast growth factor 10 (FGF10), and transforming growth factor-β1 (TGF-β1). They also elevated the expression levels of keratin genes (K31 and K85) and the ceramide synthase (CerS3) gene, crucial clinical indicators of hair health. Furthermore, they exhibited notable anti-inflammatory and anti-androgenic properties by reducing the levels of tumor necrosis factor-α (TNF-α) and androgen signaling molecules, including androgen receptor (AR) and dickkopf-1 (DKK-1) gene expression. Oral administration of WHS to C57BL/6 mice for 3 weeks confirmed its hair growth-promoting effects, improving hair growth parameters and gene expression without significant changes in hair weight. Additionally, in a human skin organoid model, WHS was found to stimulate hair formation and augment the expression of follicle markers. These findings position WHS as a promising nutraceutical for promoting hair health, as evidenced by its efficacy in both in vitro and in vivo models.

Combination Therapy with Vitamin D and Metformin: A Potential Approach to Mitigate Testicular Dysfunction in Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is a multifactorial disease that cannot be linked to a single pathway, causing the observed heterogeneity among T2DM patients. Despite this level of heterogeneity, T2DM is majorly managed by metformin (MET) monotherapy. However, recent findings have associated long-term metformin intake with progressive oxidative pancreatic β cell damage as the disease progresses. Hence, a significant number of patients treated with MET need an alternate therapy. Hence, identifying drug combinations that can effectively alleviate different diabetes complications would serve as a more promising therapy that can translate into active use. Hence, this study was designed to explore the possible synergistic effect of vitamin D and metformin on T2DM-induced testicular dysfunction. Thirty healthy male Wistar rats (weight: 120-150 g and age: 10 ± 2 weeks) were randomly divided into control, diabetes untreated (HFD+STZ), diabetes + vitamin D (1000 IU/kg), diabetes + metformin (180 mg/kg), and diabetes + vitamin D + metformin. All treatments lasted for 28 days and animals were sacrificed using IP injection of ketamine and xylaxine (40 and 4 mg/kg respectively). Vitamin D improved the ameliorative effect of metformin on T2DM-induced hyperglycemia and lipid dysmetabolism, accompanied by a significant decrease in testicular lactate dehydrogenase and lactate. Also, vitamin D + metformin significantly increased serum luteinizing hormone, follicle-stimulating hormone, testosterone, and testicular 5α reductase activities. Furthermore, vitamin D improved the anti-inflammatory and antioxidant effects of metformin by significantly decreasing T2DM-induced increase in testicular interleukin 1beta, interleukin 6, TNF-α, nitric oxide, and NF-κB and increasing T2DM-induced decrease in interleukin 10, glutathione, superoxide dismutase, catalase, GPx, and Nrf2. Vitamin D enhanced the ameliorative effect of metformin on T2DM-induced testicular dysfunction.

Terminalia bellirica (Gaertn.) Roxb. Extracts reshape the perifollicular microenvironment and regulate the MAPK pathway for androgenetic alopecia treatment

Ethnopharmacological relevanceTerminalia bellirica (Gaertn.) Roxb. (TBR), a popular herbal remedy in India and Southeast Asia, has been demonstrated to possess multiple pharmacological activities. However, systematic studies on the medicinal effects and mechanism of TBR for the androgenetic alopecia (AGA) treatment are deficient. Materials and methodsHuman Umbilical Vein Endothelial Cells (HUVECs) and testosterone-induced AGA mice were used to evaluate the hair regrowth activity of TBR extracts. Chemical constituents and potential active components of TBR extracts were analyed by UPLC-Q-TOF-MS in vitro/vivo. The hair regrowth mechanisms of TBR were elucidated through network pharmacology and experimental validation. ResultsTotally 28 chemical constituents in TBR were identified, of which 15 were predicted as potential active components for AGA therapy. TBR could significantly scavenge ROS, promote VEGF level/cell migration of HUVECs, and inhibiting type II 5α-reductase activity (the inhibit rate: 82.35 ± 1.02 %). Pharmacodynamic evaluation suggested that TBR effectively led to hair regrowth in C57BL6 mice compared to minoxidil. TBR promoted the hair follicle (HF) transition from the telogen phase to anagen phase by decreasing MDA levels, increasing VEFG expression and up-regulating phosphorylated P38/ERK protein levels in the MAPK signalling pathway. ConclusionsTBR reversed AGA via inhibiting SRD5A2 activity and stimulating the MAPK pathway. Meantime, TBR could remodel the follicle microenvironment by reducing oxidative stress and increasing angiogenesis.

18-β-Glycyrrhetinic Acid Promotes Hair Growth by Stimulating the Proliferation of Dermal Papilla Cells and Outer Root Sheath Cells, and Extends the Anagen Phase by Inhibiting 5α-Reductase.

18-β-Glycyrrhetinic acid, a major component of licorice, stimulated the proliferation of both dermal papilla cells and outer root sheath cells isolated from human hair follicles. Thus, suggesting that this compound promotes hair growth. Furthermore, this compound inhibited the activity of testosterone 5α-reductase, an enzyme responsible for converting androgen to dihydroandrogen, with an IC50 of 137.1 µM. 18-β-Glycyrrhetinic acid also suppressed the expression of transforming growth factor-β1 (TGF-β1), which shifts the hair cycle from the anagen phase to the telogen phase. It suggested that this compound may prolong the anagen phase. Based on these findings, this compound could be a potentially effective treatment for androgenetic alopecia.

Therapeutic effect of Nepenthes kampotiana Lecomte ethanol extract (Nk-EE) on androgenic alopecia through the inhibition of apoptosis and 5α-reductase activity

There is increasing interest in hair loss treatment because a growing number of people affected. Nepenthes kampotiana Lecomte is known for its anticancer effects, but its potential for preventing hair loss has not been researched. Therefore, this study focused on the hair loss prevention effects of N. kampotiana Lecomte ethanol extract (Nk-EE). The results showed that Nk-EE had a proliferative effect on human follicle dermal papilla cells and inhibited cell death. In vivo experiments using androgenic areata models showed that Nk-EE had a positive effect on a variety of biomarkers such as hair-to-skin ratio, hair type frequency, and hair thickness. The results of this study suggest that Nk-EE has potential as an effective treatment for androgenic alopecia.

In silico Analysis of Berberine as a Potential Therapeutic Approach for Various Signalling Pathways Linked to Androgenetic Alopecia

Background: Alopecia is defined by a loss of hair density and is often considered a symptom of multiple illnesses, such as infection and inflammation. Objective: The molecular mechanisms underlying the hair-promoting effects include inhibition of 5α-reductase activity, reducing the binding affinity of Dihydrotestosterone (DHT) to androgen receptors, and decreasing/down-regulating TGF-β2 activity, which have a suggestive role in androgenetic alopecia. Finasteride and minoxidil are the approved non-surgical treatment alternatives for hair loss, but they cause side effects in patients. Therefore, bioactive phytoconstituents with multiple targets can be used to find novel, secure, and efficacious hair-promoting medicinal products. Methods: This study has carried out the in silico evaluation of berberine using various software. To find possible interactions between the 5α-reductase enzyme and Transforming Growth Factor-- beta 2 (TGF-β2), a critical protein involved in the human hair development cycle, computer-aided drug discovery was employed. Results: According to in silico studies, berberine has been found to bind well to the 4K7a and 6M2N binding sites. The drug has been found to adhere to Lipinski's rule of five, and its pharmacokinetic characteristics were noteworthy. Drug-likeness and Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) properties showed appreciable results. Furthermore, berberine showed docking scores of -8.4 (5α-reductase) and -7.1 (TGF-β2), which were significantly better than minoxidil (-4.8, -3.2). In general, the drug exhibited improved binding interactions, and the possible toxicity investigations provided very little basis for risk prediction. Conclusion: The current protocol has offered experimental support for berberine's possible therapeutic use in reducing male pattern baldness. Therefore, it can be a possible target for the therapy of androgenetic alopecia through the regulation of TGF-β2 and 5α-reductase activity.

A Narrowed Look Into Plant-Derived Testosterone 5α-Reductase Inhibitors for Androgenetic Alopecia

Androgenetic alopecia (AGA) is the most prevalent cause of hair loss in men and women, resulting from a combination of genetic susceptibility and androgen hormones. Increased activity of testosterone 5α-reductase in hair follicles leads to increased synthesis of dihydrotestosterone (DHT). DHT's destructive effect on hair follicles is one of the leading reasons for hair loss. Conventional pharmacotherapeutic treatments, e.g. finasteride and minoxidil, are frequently accompanied by adverse effects and may be ineffective for certain people. Recent years have seen a rise in research on plant-derived testosterone 5α-reductase enzyme inhibitors. These herbal substances produced by various plant extracts and natural ingredients show promise in terms of fewer side effects and improved tolerability. This mini review investigates herbal testosterone 5α-reductase inhibitors for treatment AGA.

Factors associated with early-onset androgenetic alopecia: A scoping review.

Early-onset androgenetic alopecia (AGA) has been associated with various chronic conditions, including metabolic syndrome (MetS). Gaining a deep understanding of early-onset AGA may enable earlier intervention in individuals at high risks. This scoping review aims to explore the risk factors and etiology, associated conditions, and adverse effects on wellbeing in early-onset AGA. Electronic literature searches were conducted in MEDLINE, EMBASE and CENTRIAL. Eligible studies included case-control, cohort, cross-sectional, and meta-analysis studies. Selected studies needed to clearly define early-onset AGA cases or include only cases starting before the age of 40 and compare them with appropriate controls. The exclusion criteria comprised editorials, commentaries, case series, and non-systematic reviews, among others. Data extraction involved collecting study characteristics, methodologies, main outcomes, and findings. Descriptive tables were used to summarize key information and relevant variables when necessary. Among the 65 eligible articles, 67.69% were case-control studies and 78.46% evaluated only male patients. "Early-onset" was defined as cases developing before the age of 30 years in 43.08% of the studies. The Hamilton-Norwood scale was the most frequently used method for evaluating the severity of alopecia in men (69.23%). Reported risk factors for early-onset AGA included a family history of AGA, cigarette smoking, unhealthy dietary habits, and a high body mass index. Early-onset AGA may also be associated with hormonal profiles, 5α-reductase enzyme activity, androgen receptor genes, and some susceptibility loci. Comorbidities investigated included MetS, cardiovascular disease, insulin resistance, dyslipidemia, and Parkinson's disease. Men with early-onset AGA may have reduced treatment efficacy with drug like rosuvastatin, metformin or lisinopril for dyslipidemia, prediabetes, or hypertension. Additionally, young men with AGA tended to suffer from psychological issues such as anxiety and low self-esteem compared to those without hair loss. Early-onset AGA is a complex condition with various risk factors and etiology, associated comorbidities, and potential implications for treatment response and psychological health.

Microbiota modulates the steroid response to acute immune stress in male mice.

Microbiota plays a role in shaping the HPA-axis response to psychological stressors. To examine the role of microbiota in response to acute immune stressor, we stimulated the adaptive immune system by anti-CD3 antibody injection and investigated the expression of adrenal steroidogenic enzymes and profiling of plasma corticosteroids and their metabolites in specific pathogen-free (SPF) and germ-free (GF) mice. Using UHPLC-MS/MS, we showed that 4 hours after immune challenge the plasma levels of pregnenolone, progesterone, 11-deoxycorticosterone, corticosterone (CORT), 11-dehydroCORT and their 3α/β-, 5α-, and 20α-reduced metabolites were increased in SPF mice, but in their GF counterparts, only CORT was increased. Neither immune stress nor microbiota changed the mRNA and protein levels of enzymes of adrenal steroidogenesis. In contrast, immune stress resulted in downregulated expression of steroidogenic genes (Star, Cyp11a1, Hsd3b1, Hsd3b6) and upregulated expression of genes of the 3α-hydroxysteroid oxidoreductase pathway (Akr1c21, Dhrs9) in the testes of SPF mice. In the liver, immune stress downregulated the expression of genes encoding enzymes with 3β-hydroxysteroid dehydrogenase (HSD) (Hsd3b2, Hsd3b3, Hsd3b4, Hsd3b5), 3α-HSD (Akr1c14), 20α-HSD (Akr1c6, Hsd17b1, Hsd17b2) and 5α-reductase (Srd5a1) activities, except for Dhrs9, which was upregulated. In the colon, microbiota downregulated Cyp11a1 and modulated the response of Hsd11b1 and Hsd11b2 expression to immune stress. These data underline the role of microbiota in shaping the response to immune stressor. Microbiota modulates the stress-induced increase in C21 steroids, including those that are neuroactive that could play a role in alteration of HPA axis response to stress in GF animals.

Biotransformation of anabolic androgenic steroids in human skin cells

In comparison to well-known drug-metabolizing organs such as the liver, the metabolic capacity of human skin is still not well elucidated despite the widespread use of topical drug application. To gain a comprehensive insight into anabolic steroid metabolism in the skin, six structurally related anabolic androgenic steroids, testosterone, metandienone, methyltestosterone, clostebol, dehydrochloromethyltestosterone, and methylclostebol, were applied to human keratinocytes and fibroblasts derived from the juvenile foreskin. Phase I metabolites obtained from incubation media were analyzed by gas chromatography-mass spectrometry. The 5α-reductase activity was predominant in the metabolic pathways as supported by the detection of 5α-reduced metabolites after incubation of testosterone, methyltestosterone, clostebol, and methylclostebol. Additionally, the stereochemistry structures of fully reduced metabolites (4α,5α-isomers) of clostebol and methylclostebol were newly confirmed in this study by the help of inhouse synthesized reference materials. The results provide insights into the steroid metabolism in human skin cells with respect to the characteristics of the chemical structures.

Phase-specific differential regulation of mechanical allodynia in a murine model of neuropathic pain by progesterone.

Progesterone has been shown to have neuroprotective capabilities against a wide range of nervous system injuries, however there are negative clinical studies that have failed to demonstrate positive effects of progesterone therapy. Specifically, we looked into whether progesterone receptors or its metabolizing enzymes, cytochrome P450c17 and 5α-reductase, are involved in the effects of progesterone on neuropathic pain after chronic constriction injury (CCI) of the sciatic nerve in mice. Intrathecal progesterone administration during the induction phase of chronic pain enhanced mechanical allodynia development and spinal glial fibrillary acidic protein (GFAP) expression, and this enhancement was inhibited by administration of ketoconazole, a P450c17 inhibitor, but not finasteride, a 5α-reductase inhibitor. Furthermore, phospho-serine levels of P450c17 in the spinal cord were elevated on day 1 after CCI operation, but not on day 17. In contrast, intrathecal progesterone administration during the maintenance phase of chronic pain decreased the acquired pain and elevated GFAP expression; this inhibition was restored by finasteride administration, but not by ketoconazole. The modification of mechanical allodynia brought on by progesterone in CCI mice was unaffected by the administration of mifepristone, a progesterone receptor antagonist. Collectively, these findings imply that progesterone suppresses spinal astrocyte activation via 5α-reductase activity during the maintenance phase of chronic pain and has an analgesic impact on the mechanical allodynia associated with the growing neuropathy. Progesterone, however, stimulates spinal astrocytes during the induction stage of peripheral neuropathy and boosts the allodynic impact caused by CCI through early spinal P450c17 activation.

Trapa bispinosa Roxb. Pericarp Extract Exerts 5α-Reductase Inhibitory Activity in Castrated Benign Prostatic Hyperplasia Model Mice.

Trapa bispinosa Roxb. pericarp extract (TBE) has a polyphenol-rich composition and exhibits potent antioxidant and anti-glycation activities in vitro. In the present study, we investigated the inhibitory effects of TBE on 5α-reductase in vitro using LNCaP cells and in vivo using a mouse model of castrated benign prostatic hyperplasia. TBE showed concentration-dependent inhibitory effects in the 5α-reductase (5αR) activity assay. In a reporter assay using AR-Luc/LNCaP cells, TBE inhibited the activity induced by testosterone, but not that induced by dihydrotestosterone. TBE also suppressed prostate cell proliferation, prostate-specific antigens, and transmembrane protease serine 2 expression in a castrated benign prostatic hyperplasia mouse model. In addition, ellagic acid, but not gallic acid, decreased 5αR and AR-Luc activities. Together, these results suggest a potential role for TBE in benign prostatic hyperplasia through inhibition of 5αR.

초록갈파래의 모발 성장기 활성화 효능

This study was conducted to evaluate the effects of Umbraulva japonica extract on the hair growth. Treatment with U. Japonica extract significantly increased the proliferation of dermal papilla cells (DPCs), a central regulator of the hair cycle. When isolated rat vibrissa follicles were treated with U. Japonica extract for 21 d, the hair-fiber lengths of the vibrissa follicles increased. When examined the activity of 5α-reductase, which converts testosterone to dihydrotestosterone (DHT), a main cause of androgenetic alopecia, U. Japonica extract did not inhibit the 5α-reductase activity. Moreover, we found that the U. Japonica extract also significantly accelerated anagen phase in vivo. These results suggest that the U. Japonica extract has the potential to treat alopecia via the stimulation of anagen phase.

(009) Testosterone Management in Women with Hypoactive Sexual Desire Disorder Who Have Reduced 5α-Reductase Activity: A Unique Population

Abstract Introduction According to the Global Consensus Position Statement on the Use of Testosterone Therapy for Women, testosterone can significantly improve desire in menopausal women with hypoactive sexual desire disorder. Based on safety and efficacy of different formulations, the recommended treatment is 1/10th of a man’s dose, using a government approved topical testosterone gel or solution, or AndroFeme which is approved for use in menopausal women in Australia. There are, however, a subset of women without significant improvement in desire with this dose who experience improvement using higher doses of testosterone. These women have low or lower tertile dihydrotestosterone blood test values despite their total testosterone being above normal range or even in the upper tertile. The enzyme 5α-reductase converts testosterone to the more active form, dihydrotestosterone, that has a higher affinity for the androgen receptor than testosterone. 5α-reductase activity varies in different individuals. It is postulated that there are menopausal women with HSDD who have reduced 5α- reductase activity and therefore require a higher dose of testosterone from the gel or solution, or need a different testosterone formulation to realize clinical benefit. This subset of women do not appear to experience the usual adverse side effects of elevated testosterone (acne, thinning scalp hair, facial hair, aggressive behavior), in part because of low levels of dihydrotestosterone. Objectives This study examines the efficacy and safety of higher doses of testosterone using products government approved for men. Methods This is a retrospective chart review of menopausal women who were provided menopause management at our clinic focusing on women for whom 1/10th of a man’s dose of gel or solution did not provide symptom relief. Options included increasing the dose of gel or solution, or administration of an alternative delivery system of FDA approved (for men) testosterone including insertion of one or two 75 mg testosterone pellets (Testopel) or weekly intramuscular injection of testosterone cypionate (100 mg/ml – 0.1 ml or 10 mg). Results A total of 11 women (mean age 58 +/− 6 years) failed the usual 1/10th dose of topical testosterone gel for treatment of HSDD. Using testosterone pellet therapy, with 1-2 pellets implanted every 4-6 months, 6 patients had excellent desire as well as energy and self-confidence; 4 patients had excellent clinical response to weekly IM testosterone administration; 1 had improved symptoms by increasing the gel to 1 tube/4 days. While these treatments resulted in systemic levels of total testosterone outside the normal range for women (100 – 200 ng/dl), dihydrotestosterone values remained low or in the lower tertile (mean value 36 +/− 8 ng/dl; normal range 30 – 80 ng/dl). In general, side effects to be expected with higher doses of testosterone were not experienced despite elevated testosterone values. No patient complained of side effects consistent with excess testosterone other than mild facial hair. Conclusions In some women with reduced 5α-reductase activity, higher testosterone levels result in improved quality of life without expected negative side effects from higher physiologic levels of testosterone. Disclosure No.

5α-Reductase Inhibitory Potential of <i>Hibiscus rosa sinensis</i>: Effective for the Management of Alopecia

The condition known as male pattern hair loss and benign prostatic hyperplasia are both treated with a family of drugs known as 5 alpha reductase (5α-reductase) inhibitors. This study shows that the flower of Hibiscus rosa sinensis has 5α-reductase inhibitory action that is helpful in the treatment of androgenic diseases. Phytochemical screening was done using petroleum ether, methanol, and water extracts to identify the phytochemical group present. Then, using quercetin as a reference flavonoid component, the Total Flavonoid Content (TFC) was assessed using a colorimetric technique. The 5α-reductase inhibitory activity was evaluated using several extracts and compared to the well-known 5α-reductase inhibitor finasteride. Finally, the inhibition of different extracts to the enzyme was assessed using a biochemical approach to measure the activity of 5α-reductase. It was determined that the IC<sub>50</sub> value of Hibiscus rosa sinensis methanolic extract, 146.048 ± 0.453 (μg/mL) and quercetin (a chemical biomarker of the plant material) 141.426 ± 1.578 (μg/mL), were promising candidates for future investigation into their antiandrogenic activities.

Biochemical and Histopathological evaluation of prostatic tissue under effect of Pterostilbene in benign prostatic hyperplasia rat model

Background: Benign prostatic hyperplasia [BPH] is the urologic condition that affects elderly men the most frequently Benign prostatic hyperplasia. Benign prostatic hyperplasia must be distinguished from
 lower urinary tract symptoms and benign prostatic enlargement. which refers to an enlarged prostate, benign prostatic hyperplasia is a purely histological term the development, maintenance, and secretory activity of the prostate and other sex-accessory tissues are stimulated by the presence of certain hormones and growth factors. the pathophysiology of Benign prostatic hyperplasia is significantly influenced by the activity of the enzyme 5α-reductase. It's important to remember that 5-αreductase is responsible for creating Dihydrotestosterone a stronger androgen. Pterostilbene Mostly found in blueberries and grapes and pterostilbene substance with a number of biological properties including anticancer properties. pterostilbene is a lipid-soluble molecule that exists in both cis and trans forms with the latter being more prevalent. The conventional medication for Benign prostatic hyperplasia utilized in this trial was finasteride which inhibits the 5α-reductase enzyme and lowers the amount of Dihydrotestosterone.
 Methods: Forty-eight male rats were divided into six groups; the control group consisted of eight rats who received subcutaneous injections of oil vehicle for a period of 42 days. The induction group consisted of eight rats who received subcutaneous injections of testosterone propionate for a period of fourteen days. The finasteride group consisted of eight rats who received finasteride 0.44 mg/kg by oral gavage for a period of twenty-eight days following the induction of Benign prostatic hyperplasia and Pterostilbene 200 group included 8 rats were given pterostilbene 200mg/kg by oral gavage for 28 days after 14 days of Benign prostatic hyperplasia induction. pterostilbene 100 group included 8 rats were given a pterostilbene 100mg/kg per day kg by oral gavage for 28 days after 14 days of induction Benign prostatic hyperplasia dose and the resveratrol group included 8 rats were given a resveratrol 100mg/kg per day kg by oral gavage for 28 days after 14 days of induction Benign prostatic hyperplasia After twenty-eight days.
 Results: Histological section of prostate Pterostilbene 200 were similar those in control negative revealed numerous variable sizes alveoli that filled with homogenous eosinophilic secretion, had normal epithelial and stromal tissue.
 Conclusion: Pterostilbene have a potent anti-proliferative effect by decrease the hyperplastic nodules for prostate and return epithelial cell to normal and have a very good scavenging activity for free radical [very good as antioxidant] in compare with Vitamin c and resveratrol.
 Aim of study: evaluate the effect of Pterostilbene as Anti proliferative on Benign prostatic hyperplasia and assess the antioxidant activity for Pterostilbene by DPPH Assay.

Trajectories of Allopregnanolone and Allopregnanolone to Progesterone Ratio across the Six Subphases of Menstrual Cycle.

Background: Allopregnanolone is one of the most studied neuroactive steroids; yet, despite its relevance to neuropsychiatric research, it is not known how it, as well as its ratio to progesterone, varies across all six subphases of the menstrual cycle. Two enzymes-5α-dihydroprogesterone and 5α-reductase-convert progesterone to allopregnanolone, and, based on immunohistochemical studies in rodents, the activity of 5α-reductase is considered the rate-limiting step in the formation of allopregnanolone. It is not clear, however, whether the same phenomenon is observed across to the menstrual cycle, and, if so, at what point this takes place. Methods: Thirty-seven women completed the study during which they attended eight clinic visits across one menstrual cycle. We analyzed their allopregnanolone and progesterone serum concentrations using ultraperformance liquid chromatography-tandem mass spectrometry, and we implemented a validated method to realign the data from the original eight clinic study visits, following which we imputed the missing data. Hence, we characterized allopregnanolone concentrations, and the ratio of allopregnanolone:progesterone at six menstrual cycle subphases: (1) early follicular, (2) mid-follicular, (3) periovulatory, (4) early luteal, (5) mid-luteal, and (6) late luteal. Results: There were significant differences in allopregnanolone levels between (1) early follicular and early luteal, (2) early follicular and mid-luteal, (3) mid-follicular and mid-luteal, (4) periovulatory and mid-luteal, and (5) mid-luteal and late luteal. We detected a sharp drop in allopregnanolone:progesterone ratio in the early luteal subphase. Within the luteal subphase, the ratio was the lowest in the mid-luteal subphase. Conclusions: Allopregnanolone concentrations are the most distinct, relative to the other subphases, in the mid-luteal subphase. The shape of the allopregnanolone trajectory across the cycle is similar to that of progesterone; however, the proportion of the two neuroactive steroid hormones is drastically different due to enzymatic saturation, which takes place at the start of the early luteal subphase, but continuing through, and peaking, in the mid-luteal subphase. Hence, the estimated activity of 5α-reductase decreases, but does not cease, at any point across the menstrual cycle.

Targeting HMGB1/PI3K/Akt and NF-κB/Nrf-2 signaling pathways by vildagliptin mitigates testosterone-induced benign prostate hyperplasia in rats

Benign prostatic hyperplasia (BPH) is a prevalent illness in older adults. It is well-recognized that testosterone is essential in the onset of BPH. Vildagliptin (Vilda), a dipeptidyl peptidase-IV inhibitor, has been shown to have anti-inflammatory and antioxidant effects. In this study, we studied the effects of vildagliptin on testosterone-induced BPH in rats and its underlying mechanisms. Forty male Wistar rats were allocated into four groups (n = 10): CTRL, Vilda, BPH, and BPH + Vilda groups. Our results revealed that vildagliptin treatment considerably lessened the prostate weight, prostate index, serum levels of prostate-specific antigen, 5α-reductase activity, and DHT levels compared to the testosterone group. Furthermore, vildagliptin treatment inhibited the expression of HMGB1, PI3K/Akt/NF-κB, and TNF-α signaling pathways in the prostate tissue of diseased rats. Additionally, vildagliptin treatment increased the expression of Nrf-2 and HO-1, reduced GSH levels, and lowered MDA levels. Besides, vildagliptin noticeably scaled up the level of cleaved caspase-3 enzyme and, conversely, the protein expression of proliferating cell nuclear antigen (PCNA). Correspondingly, vildagliptin counteracts testosterone-induced histological irregularities in rats' prostates. These findings suggest that vildagliptin may be a potential prophylactic approach to avoid BPH.

PROCESS VALIDATION OF BETA-SITOSTEROL HAIR GEL FORMULATION AND EVALUATION OF 5 ALPHA REDUCTASE INHIBITION IN VITRO FOR THE TREATMENT OF ANDROGENETIC ALOPECIA

Objective: The present study was aimed to develop topical gel containing β-sitosterol using carbopol 940 as a gelling agent and to investigate 5 alpha reductase (5α-reductase) inhibitory activity of suitable gel formulation and compare it with a commercial product used topically for alopecia. Methods: Three different batches of β-sitosterol hair gel formulation were manufactured and evaluated. Additionally, the 5α-reductase inhibitory activity of the prepared formulation, finasteride as a positive control, was evaluated and compared to the commercial herbal formulation used. Results: According to the analytical findings of three different batches, the gel formulation is good in appearance, homogeneous, and easily spreadable. Based on findings from HPLC and HPTLC, the amount of β-sitosterol in those formulations complies with the label claim. By checking different critical parameters of those batches, we established the manufacturing process method validation and the process reproducibility. In vitro results showed the good 5α-reductase inhibitory potential of prepared gel formulation and then commercial product. The IC50 value of the prepared formulation was 118.960±0.634 (µg/ml) and standard beta-sitosterol 88.854±0.70 (µg/ml), whereas Finasteride (positive control) 224.372±3.103 (ng/ml). Conclusion: Thus, β-sitosterol formulation utilises a straightforward, low-cost production, less time-consuming process with minimal facility and equipment requirements. The formulation may be a promising candidate for future investigation into their antiandrogenic activities.

Assessment of the anti-hair loss potential of Camellia japonica fruit shell extract in vitro.

Hair loss is caused by various factors. Impacts of these factors are often overlapped and intensified. Currently, mitigation of hair loss is being studied by proliferating dermal papilla cells (DPCs) and inhibiting deleterious factors such as dihydrotestosterone (DHT) and oxidative stress on hair growth. Camellia japonica (C.japonica) fruit shell is a discarded part. Its biological activity remains to be elucidated. In this study, we investigated the capacity of C.japonica fruit shell extract (CJFSE) for hair loss mitigation. MTT assay, spheroid culture and quantitative RT-PCR were performed to observe the proliferative effect of CJFSE on hair follicle dermal papilla cells (HFDPCs). Effects of CJFSE on DHT-induced hair loss were confirmed by Dkk-1 ELISA, β-galactosidase (β-gal) and 5α-reductase activity assay. In addition, effects of CJFSE on oxidative stress were confirmed through DPPH and ROS production assays. CJFSE increased the proliferation and spheroid size of HFDPCs. Expression levels of VEGF-A, Wnt-1, c-Myc and Cyclin D1 were upregulated by CJFSE. CJFSE also suppressed 5α-reductase activity and DHT-induced decrease in cell proliferation, Dkk-1 secretion and β-gal activity. Moreover, CJFSE showed DPPH scavenging activity and ameliorated hydrogen peroxide-induced ROS production and β-gal activity. Finally, gallic acid and protocatechuic acid were observed in CJFSE through HPLC analysis. CJFSE has the potential to alleviate hair loss by promoting hair cell growth and suppressing effects of DHT and oxidative stress on hair.