Background: Lower urinary tract symptoms (LUTS) are prevalent among aging men and negatively affect quality of life. Salvia miltiorrhiza extract (SAGX), which exhibits anti-inflammatory and antioxidant properties, has been developed as a functional ingredient to improve LUTS. However, comparative clinical data against established standards, such as saw palmetto, are currently lacking. Objectives: To compare the efficacy and safety of SAGX with saw palmetto extract in men with LUTS. Methods: In this randomized, parallel-group pilot study, 30 men with LUTS were assigned to receive either 400 mg of SAGX or 320 mg of saw palmetto extract once daily for 12 weeks. The primary outcome was the change in the International Prostate Symptom Score (IPSS) and the LUTS-related quality-of-life (QoL) score. Secondary outcomes included changes in the erectile function assessed using the International Index of Erectile Function (IIEF). Safety was evaluated by monitoring adverse events. Results: SAGX supplementation resulted in a significantly greater reduction in total IPSS compared with the saw palmetto group (p = 0.031), with notable improvements in storage symptoms (p = 0.003) and QoL (p = 0.035). Erectile function also improved significantly in the SAGX group (p = 0.005). All adverse events were mild and transient, with treatment-related events occurring less frequently in the SAGX group. Conclusions: Although this study was a pilot study with a limited cohort, these findings provide preliminary evidence for the use of SAGX as a functional ingredient for supporting urinary health in men with LUTS.

While androgenetic alopecia (AGA) is primarily driven by excessive 5-α reductase (5-αR) activity, further mechanisms also contribute to the development of AGA and other hair loss disorders. Here, we explored the properties of the proprietary lipidosterolic extracts of the plant Serenoa repens (LSESr), also known as Saw Palmetto, focusing on USPlus® DERM Bioactive Fatty Acids (USPlus® DERM). USPlus® DERM contains concentrated levels of bioactive free fatty acids (FFAs) that are integral lipids found in the hair shaft and modulate pathways relevant to hair follicle (HF) function. Therefore, USPlus® DERM promises to have both 5-αR-dependent and also -independent hair growth-promoting effects. Here, we initially confirmed the 5-αR inhibitor activity of USPlus® DERM in primary human hair follicle dermal papilla cells. USPlus® DERM exhibited a more potent 5-αR inhibition than a standard, commercially available saw palmetto extract and a standardized LSESr meeting the US Pharmacopoeia monograph, with IC50 values of 0.39, 29.1 and 9.1 μg/mL respectively. To explore potential 5-αR-independent responses, USPlus® DERM was administered at two different concentrations, 0.4 and 10 μg/mL, to androgen-independent, 'clinically healthy' full-length HFs ex vivo obtained from the occipital scalp of male donors, in the absence of testosterone. Interestingly, USPlus® DERM at 0.4 μg/mL significantly reduced the number of melanin clumps, regarded as signs of organ culture mediated stress conditions. Despite inter-donor variations, USPlus® DERM prolonged anagen ex vivo, particularly at the low concentration, evidenced by a significant reduction in the hair cycle score and the tendency to boost hair matrix keratinocyte proliferation (Ki-67[+]cells). USPlus® DERM did not affect dermal papilla inductivity, as measured by versican expression and alkaline phosphatase activity. While the percentage of K15[+] epithelial HF stem cells (eHFSC) remained unaffected, 0.4 μg/mL USPlus® DERM tendentially enhanced K15 expression and reduced the number of Ki-67[+]K15[+] cells, indicating reinforcement of the eHFSCs niche. These preliminary findings suggest that USPlus® DERM has the potential to promote hair growth and to enhance HFSC stemness in the 'clinically predictive' HF organ culture model, independently from 5-αR inhibition. Thus, USPlus® DERM deserves to be further investigated as an anti-hair loss strategy, for not only AGA management but also other hair loss disorders.

Topical hair growth supplements in the form of hair growth serums, oils, and shampoos have flooded the cosmeceutical market. The gullible masses are targeted with sponsored marketing gimmicks through social media platforms. This review article brings to light the most hyped active ingredients or peptides in these products along with their clinical evidence available in the literature. The topical actives include Redensyl, Procapil, Capixyl, Baicapil, AnaGain, onion juice, coffee extract, saw palmetto extract, pumpkin seed oil (PSO), and rosemary oil. PubMed, Google Scholar, and Google databases were searched with the keywords: topical, hair growth, hair loss, and the respective active agents. Twenty-four relevant articles and technical files were extracted and reviewed. They have been studied mostly as combined formulations with other agents in randomized controlled trials or prospective cohort studies and have shown promising results. However, most of the studies have limited sample size, lack of comparison with standard therapies, nonuniformity between study groups, nondisclosure of the type of alopecia treated, and conflicts of interest. These topicals with their less significant side effect profile may find their use as an add-on therapy or as an alternative in patients not tolerating standard therapies. In this fast-growing commercialized world, it is imperative that we remain vigilant and understand the pros and cons of these products and ultimately guide our patients to the right track.

Selected phenotypes of dried maca (Lepidium peruvianum) hypocotyls and supercritical CO2 extract (USPlus[®]) of saw palmetto (Serenoa repens) were used to determine their targeted, cytotoxic action in prostate cancer cells. Fingerprinting by HPLC-MS and PCA analysis showed compositional differences in glucosinolates, amides, macamides, and other alkaloids, which varied based on the color and the size of hypocotyls. These phytochemical differences translated into a higher antioxidant potential of red maca than black maca samples. The greatest COX-2 inhibition was demonstrated with a combination of red maca: saw palmetto (67%:33%) and red maca: saw palmetto: black maca (25%:50%:25%). The LNCaP androgen-dependent prostate cancer cell line was the most sensitive to the three-component mixture of black, red maca, and saw palmetto treatment. This combination provided the most abundant set of high-activity metabolites, and is worthy of consideration in further clinical applications and future in-depth study.

Saw palmetto extract (SPE) is the most commonly used supplement for the treatment of lower urinary tract symptoms (LUTS), but most evidence is for those with LUTS, and little data is verifying its effectiveness for those who do not have the disease but are troubled by symptoms. The purpose of this study was to examine the effect of SPE on the improvement of urinary frequency problems that present stress due to urinary urgency in daily life, among healthy Japanese adults aged ≥50 years who are not diagnosed with benign prostatic hyperplasia or overactive bladder. They were randomly assigned to the SPE group or placebo group (34 participants per group) using a computerized random number generator. Each participant was instructed to take one capsule containing SPE (320 mg) or placebo every day for 12 weeks. Subjective symptoms were assessed using the overactive bladder questionnaire, and the score of symptom bother by frequent urination during the daytime hours was set as the primary outcome. The other outcomes were subjective urinary symptoms and urinary frequencies. The final efficacy analysis dataset was per protocol set, and 33 participants in each group were analyzed. After SPE intervention for 12 weeks, the score of symptom bother by frequent urination during the daytime hours was significantly improved and the daytime frequency of urination assessed using the urinary log was significantly decreased. The consumption of SPE improved urinary frequency-related quality of life such as bother of urinary symptoms in healthy Japanese adults (UMIN000045334).

Benign prostatic hyperplasia (BPH) is a prevalent urological condition that predominantly affects the geriatric male population, resulting in lower urinary tract symptoms. Saw palmetto is a traditional Chinese medicine for treating BPH. This study aimed to investigate the potential therapeutic mechanisms of saw palmetto in BPH treatment. The active ingredients and potential targets of saw palmetto were obtained through the TCMSP database. BPH-related targets were retrieved from the GeneCards database. PPI, GO, and KEEG analyses were performed to predict the potential therapeutic mechanism. The active ingredient-common target and common target-pathway networks were constructed by Cytoscape software. Molecular docking and cellular experiments were carried out to further validate the potential mechanism. We obtained 13 active components in saw palmetto and 56 common targets in BPH treatment. KEEG analysis showed that the estrogen signaling pathway was the most enriched and exhibited a close association with BPH. PPI analysis, along with ingredient-target and target-pathway network analyses, indicated that stigmasterol was the core ingredient and PGR, NCOA1, and NCOA2 were identified as the hub genes mediating the effects of saw palmetto against BPH. In addition, molecular docking showed that stigmasterol had strong binding to PGR, NCOA1, and NCOA2. Cellular experiments revealed that stigmasterol significantly increased the percentage of BPH-1 cells in the G0/G1 phase and inhibited cell viability and division. Furthermore, it notably reduced the expression of PGR, NCOA1, and NCOA2. Saw palmetto might inhibit cell viability and division by suppressing the expression of PGR, NCOA1, and NCOA2, thereby playing a therapeutic role in treating BPH.