Effect of Black Cumin (Nigella sativa) on Prostate Health: Narrative Review

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Alzahrani" }, { "@type": "Person", "name": "Ibrahim Abunohaiah" }, { "@type": "Person", "name": "Yousuf Altuwaijry" }, { "@type": "Person", "name": "Muath Alahmadi" }, { "@type": "Person", "name": "Osama Qasim" }, { "@type": "Person", "name": "Abdulaziz Alzahrani" }, { "@type": "Person", "name": "Shamshad Begum Loni" }, { "@type": "Person", "name": "Mohammed Shareef" }, { "@type": "Person", "name": "Raed Almannie" }, { "@type": "Person", "name": "Saleh Binsaleh" } ], "publisher": { "@type": "Organization", "name": "F1000Research", "logo": { "@type": "ImageObject", "url": "https://f1000research.com/img/AMP/F1000Research_image.png", "height": 480, "width": 60 } }, "image": { "@type": "ImageObject", "url": "https://f1000research.com/img/AMP/F1000Research_image.png", "height": 1200, "width": 150 }, "description": "A growing amount of research is shedding light on nutrient-rich foods and nutritional supplements’ potential health and disease-preventative advantages. Black cumin (Nigella sativa L.), an esteemed nutraceutical herb, is well-known for its multiple health advantages among health-conscious individuals, researchers, and pharmaceutical businesses. Black cumin and its principal bioactive ingredient, thymoquinone (TQ), have been found to lower oxidative stress and inflammation, while also enhancing immunological function, cellular viability, and energy metabolism. They protect against metabolic, cardiovascular, digestive, hepatic, renal, pulmonary, reproductive, and neurological diseases, as well as cancer. Black cumin works as a countermeasure to minimize the toxicity and side effects of pharmaceuticals. Furthermore, the possible effects of black cumin on prostate health and disorders like benign prostatic hyperplasia and prostate cancer are not well understood. This narrative review seeks to reveal knowledge gaps. This study intends to guide future research into the possible uses of black cumin and TQ in prostate health and illness." } { "@context": "http://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": "1", "item": { "@id": "https://f1000research.com/", "name": "Home" } }, { "@type": "ListItem", "position": "2", "item": { "@id": "https://f1000research.com/browse/articles", "name": "Browse" } }, { "@type": "ListItem", "position": "3", "item": { "@id": "https://f1000research.com/articles/13-229", "name": "Effect of Black Cumin (Nigella sativa) on Prostate Health: Narrative..." } } ] } Home Browse Effect of Black Cumin (Nigella sativa) on Prostate Health: Narrative... ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article Alzahrani MA, Abunohaiah I, Altuwaijry Y et al. Effect of Black Cumin ( Nigella sativa ) on Prostate Health: Narrative Review [version 2; peer review: 4 approved with reservations] . F1000Research 2025, 13 :229 ( https://doi.org/10.12688/f1000research.145024.2 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Review Revised Effect of Black Cumin ( Nigella sativa ) on Prostate Health: Narrative Review [version 2; peer review: 4 approved with reservations] Meshari A. Alzahrani https://orcid.org/0000-0002-8504-7486 1 , Ibrahim Abunohaiah 2 , Yousuf Altuwaijry 3 , [...] Muath Alahmadi https://orcid.org/0009-0008-9191-9915 4 , Osama Qasim 4 , Abdulaziz Alzahrani 5 , Shamshad Begum Loni 6 , Mohammed Shareef 7 , Raed Almannie 2 , Saleh Binsaleh https://orcid.org/0000-0001-8946-4749 2 Meshari A. Alzahrani https://orcid.org/0000-0002-8504-7486 1 , Ibrahim Abunohaiah 2 , [...] Yousuf Altuwaijry 3 , Muath Alahmadi https://orcid.org/0009-0008-9191-9915 4 , Osama Qasim 4 , Abdulaziz Alzahrani 5 , Shamshad Begum Loni 6 , Mohammed Shareef 7 , Raed Almannie 2 , Saleh Binsaleh https://orcid.org/0000-0001-8946-4749 2 PUBLISHED 21 Feb 2025 Author details Author details 1 Urology, College of Medicine, Majmaah University, Al Majmaah, Riyadh Province, 11952, Saudi Arabia 2 Urology, Faculty of Medicine, King Saud University,, Riyadh, Riyadh Province, 11461, Saudi Arabia 3 College of Medicine, Majmaah University, Al Majmaah, Riyadh Province, 11952, Saudi Arabia 4 College of Medicine, Umm Al-Qura University, Mecca, Makkah Province, 24381, Saudi Arabia 5 Urology, Prince Mansour Military Hospital, Taif, Makkah Province, 26526, Saudi Arabia 6 Basic Medical Science, Majmaah University, Al Majmaah, Riyadh Province, 11952, Saudi Arabia 7 Urology, King Fahd Hospital, Madinah, Madinah, 42210, Saudi Arabia Meshari A. Alzahrani Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Ibrahim Abunohaiah Roles: Writing – Original Draft Preparation Yousuf Altuwaijry Roles: Writing – Original Draft Preparation Muath Alahmadi Roles: Writing – Original Draft Preparation Osama Qasim Roles: Writing – Original Draft Preparation Abdulaziz Alzahrani Roles: Writing – Original Draft Preparation Shamshad Begum Loni Roles: Writing – Original Draft Preparation Mohammed Shareef Roles: Writing – Original Draft Preparation Raed Almannie Roles: Validation, Visualization, Writing – Review & Editing Saleh Binsaleh Roles: Validation, Visualization, Writing – Review & Editing OPEN PEER REVIEW DETAILS REVIEWER STATUS This article is included in the Oncology gateway. Abstract A growing amount of research is shedding light on nutrient-rich foods and nutritional supplements’ potential health and disease-preventative advantages. Black cumin ( Nigella sativa L. ), an esteemed nutraceutical herb, is well-known for its multiple health advantages among health-conscious individuals, researchers, and pharmaceutical businesses. Black cumin and its principal bioactive ingredient, thymoquinone (TQ), have been found to lower oxidative stress and inflammation, while also enhancing immunological function, cellular viability, and energy metabolism. They protect against metabolic, cardiovascular, digestive, hepatic, renal, pulmonary, reproductive, and neurological diseases, as well as cancer. Black cumin works as a countermeasure to minimize the toxicity and side effects of pharmaceuticals. Furthermore, the possible effects of black cumin on prostate health and disorders like benign prostatic hyperplasia and prostate cancer are not well understood. This narrative review seeks to reveal knowledge gaps. This study intends to guide future research into the possible uses of black cumin and TQ in prostate health and illness. READ ALL READ LESS Keywords Black cumin, Nigella sativa, Black seed, Thymoquinone, Prostate. Corresponding Author(s) Meshari A. Alzahrani ( [email protected] ) Close Corresponding author: Meshari A. Alzahrani Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2025 Alzahrani MA et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Alzahrani MA, Abunohaiah I, Altuwaijry Y et al. Effect of Black Cumin ( Nigella sativa ) on Prostate Health: Narrative Review [version 2; peer review: 4 approved with reservations] . F1000Research 2025, 13 :229 ( https://doi.org/10.12688/f1000research.145024.2 ) First published: 27 Mar 2024, 13 :229 ( https://doi.org/10.12688/f1000research.145024.1 ) Latest published: 21 Feb 2025, 13 :229 ( https://doi.org/10.12688/f1000research.145024.2 ) Revised Amendments from Version 1 We made necessary changes in the text only in the abstract, introduction, discussion, and conclusion based on requests by the reviewer assigned to review our manuscript. There are no changes or updated figures, updates to the author list, or additional data or code. We made necessary changes in the text only in the abstract, introduction, discussion, and conclusion based on requests by the reviewer assigned to review our manuscript. There are no changes or updated figures, updates to the author list, or additional data or code. See the authors' detailed response to the review by Rodney Hull READ REVIEWER RESPONSES Introduction The prostate, a small gland in the male reproductive system, is responsible for creating seminal fluid, which nourishes and transports sperm. However, prostate-related disorders, such as benign prostatic hyperplasia (BPH) and prostate cancer (PCa), are common among older men. 1 – 3 As traditional therapies progress, complementary and alternative techniques are being investigated to promote prostate health. One such strategy is using Black Cumin, formally known as Nigella sativa , which has received interest because of its possible impact on prostate health. 4 – 7 The plant known as black cumin belongs to the Ranunculaceae family. It is indigenous to some parts of Asia and the Middle East and has a long history of use in traditional medicine and cuisine. Black cumin is also known as black seed, black caraway, kalonji, and the Habitat of Al-Baraka, or Al-Habba Al-Saouda. 6 , 8 – 11 This plant contains small, black seeds, which have been used medicinally for millennia ( Figure 1 ). 12 These seeds have a particular flavor and scent and are frequently used as spices in cuisine. The oil produced from black cumin seeds has a variety of culinary and herbal applications. 8 , 9 Figure 1. Black Cumin ( Nigella sativa ), (A) flower, (B) seeds, (C) harvested seeds. This figure has been reproduced with permission from Ref. 12 . For generations, black cumin has been recognized for its therapeutic virtues and used in traditional medicine. The seeds have a high concentration of bioactive chemicals that provide numerous health benefits. 9 Recent research has highlighted black cumin’s possible influence on the prostate, sparking interest in its role in prostate-related disorders. 6 , 9 , 13 Thymoquinone (TQ) (2-isopropyl-5-methyl-benzoquinone) 14 is the main bioactive component in the volatile oil isolated from black seeds ( Figure 2 ). 15 Figure 2. (a) Nigella sativa seeds (black seeds). (b) The chemical structure of thymoquinone; 2-isopropyl-5-methyl-1,-benzoquinone (C 10 H 12 O 2 ). This figure has been reproduced with permission from Ref. 15 . In addition to TQ, black cumin seeds contain thymoquinones and flavonoids. These components are thought to contribute to the health advantages of black cumin. It has traditionally been used to treat a variety of health issues, including digestive, respiratory, cardioprotective, antidiabetic, anti-inflammatory, and antiviral effects, immune system function, nephroprotective, and hepatoprotective properties; antioxidant activity; skin problems; and renal and prostate conditions. 4 – 9 , 15 – 21 It is crucial to highlight that, while black cumin has a long history of traditional use and promising preliminary study, more extensive research is required to completely understand its possible health effects and establish its safety and efficacy. Among the different choices, black cumin has emerged as a viable candidate for health improvement due to its low toxicity and multiple modes of action. 21 This review looks at the developing data for the effects of black cumin on prostate health. While conventional medical treatments remain the cornerstone of managing prostate diseases such as BPH and PCa, research into the potential advantages of natural substances such as black cumin may pave the way for new therapeutic methods. This article dives into the present level of knowledge about the effects of black cumin on prostate health, focusing on both its traditional use and the scientific evidence that supports its potential benefits. As our understanding grows, we will have a more complete picture of the role of black cumin in prostate health, revealing light on its potential as a complimentary strategy to known conventional therapies. 2. Methods The literature search was conducted in scientific databases MEDLINE/PUBMED, by using keywords such as “black cumin” and “black seed,” “ N. sativa ” and “active compounds,” “ N. sativa ” and “Thymoquinone” and “prostate cancer,” “benign prostatic hyperplasia, “prostate cancer.” All the included articles published in English till 2023 were selected. Two senior authors (M.A.A. and R.M.) were individually tasked with gathering the relevant information. These details included author identities, year of publication, subjects involved, type of intervention, and the main outcomes of studies reporting the potential effect of black cumin on prostate health. If disagreements arose, a third reviewer reached a consensus. Our approach did not impose any constraints on the publication dates of the articles. We eliminated non-English literature, articles lacking relevance, duplicates, abstract-only publications, articles without full-text availability, reviews, and books. After identifying pertinent articles, we scrutinized the reference lists of these articles and recent reviews to ensure comprehensive coverage, avoiding omissions. We identified 24 articles related to our search. Following the predetermined inclusion and exclusion criteria, 13 articles were excluded because they did not meet our requirements. Ultimately, 11 articles fulfilled our criteria, reporting on Black cumin and its effects on the prostate, which formed the basis for our review. A flowchart of the article selection process is shown in Figure 3 . Figure 3. Flow diagram representing the study article selection. 3. Results Eleven relevant articles were published between 2007 and 2021. Ten articles reported the effect of Black cumin on PCa, while one article was on BPH. Most of the studies were experimental in vivo and in vitro. The extracted data on the potential benefits of Black cumin on the prostate based on human and animal models are summarized in Table 1 and Table 2 . Table 1. Subject characteristics treated with black cumin ( Nigella sativa ). Author/study location/year Prostate cell experimental model Subjects Treatment with Doses Kou, China (2017) 22 PC-3, DU-15 Vitro TQ (0.1–30 μM) for 2 hours. Dirican, Turkey (2015) 23 PC-3 and DU-15 Vitro Combination of docetaxel and TQ in DU-15 hormone- and drug-refractory prostate cancer cells and their effects on PI3K and ERK signaling pathways Kus, Turkey (2018) 24 LNCaP Vitro N. sativa oil for 2 and 8 h Koka, USA (2010) 25 PC-3 and C4-2B Vitro TQ (25-150 micromol/L) for 2-8 h Zubair, India (2013) 26 PC3, LNCaP, DU145 and C42B Vivo TQ 25 mM Kaseb, USA (2007) 27 PC-3, LNCaP, DU-15, DU145, and C4-2B Vitro and in vivo TQ (0–100 Amol/L) 2 to 8 h Yi, USA (2008) 28 PC-3 Vitro and in vivo TQ 6 mg/kg/day Dawaba, Egypt (2019) 29 PC-3 Vitro N. sativa oil 10 mg/ml Alshyarba, Saudi Arabia (2021) 30 PC-3, DU-15 and LNCaP Vitro TQ (dose not reported) Dirican, Turkey (2014) 31 PC3 and DU-15 Vitro TQ (10 μM) Sadeghimanesh, Iran (2021) 6 BPH model Vivo 400 and 800 mg/kg N. sativa oil Table 2. Potential effect of black cumin ( Nigella sativa ) on prostate disease. Author/study location/year Major findings (including molecular changes) Main outcome Kou, China (2017) 22 - TQ substantially arrested the proliferation of prostate cancer. - TQ inhibited the migrating and invading capability of prostate cancer DU-15 and PC-3 cells. - TQ also downregulated the expression of TGF-β. Antineoplastic activity Dirican, Turkey (2015) 23 - TQ promoted apoptosis by modulating the PI3K-AKT pathway in human prostate carcinoma DU-15 and PC-3 cells. - TQ blocking of the PI3K/Akt signaling pathway. Reducing chemotherapy (docetaxel) dosages and its adverse effects in cases with CRPC Kus, Turkey (2018) 24 - TQ exhibits a robust concentration and time-dependent impact on diminishing cancer cell viability through apoptosis in LNCaP prostate cancer cells. Antineoplastic activity Koka, USA (2010) 25 - TQ significantly up-regulated the expressions of growth arrest and DNA damage-inducible gene (GADD45a) and apoptosis-inducing factor-1 and down-regulated the expressions of several Bc12-related proteins, such as BAG-1, Bcl2, Bcl2A1, Bcl2L1, and BID. - The primary reason for cell death induced by TQ is the heightened generation of ROS and the reduction in levels of GSH. Antineoplastic activity Zubair, India (2013) 26 - TQ causes DNA oxidative damage, counteracted by copper-chelating agents and antioxidants. - It affects cellular copper in prostate cancer cells, leading to prooxidant-induced cell death. Antineoplastic activity Kaseb, USA (2007) 27 - TQ effectively inhibits DNA synthesis, proliferation, and viability in cancerous prostate epithelial cells (LNCaP, C4-2B, DU-15, and PC-3), while not impacting non-cancerous BPH-1 cells. - This effect was attributed to the down-regulation of AR and E2F-1 (a transcription factor). Antineoplastic activity Yi, USA (2008) 28 - TQ blocked angiogenesis and tumor growth, even at low doses with minimal side effects. - TQ selectively affected endothelial cells, inhibiting proliferation, migration, and inducing apoptosis. - TQ suppressed extracellular signal-regulated kinase activation by vascular endothelial growth factor but didn't affect vascular endothelial growth factor receptor 2 activation. Antineoplastic activity Dawaba, Egypt (2019) 29 - Nigella sativa essential oil in vitro cytotoxicity testing revealed that the oil encapsulated in nanoparticles is more effective in reducing cancer cell viability compared to the unencapsulated oil. Antineoplastic activity Alshyarba, Saudi Arabia (2021) 30 - TQ has the capacity to block the metastatic processes induced by IL-7 in prostate cancer cells. Antineoplastic activity Dirican, Turkey (2014) 31 - The synergistic combination of ZA and TQ inhibits cell viability and induces apoptosis in PC-3 and DU-15 prostate cancer cells. Compared to cytotoxic agents, it exhibits a minimal profile of hematological and non-hematological toxicity. Sadeghimanesh, Iran (2021) 6 - Significant decrease in PI, PV, DHT concentration, PSA, and serum MDA level, and also significantly increased serum antioxidant capacity. Anti-BPH effects Table 1 shows the reported articles from a different continent. A xenograft human prostate cancer cell line model has been used in most studies. All studies used the active component of Nigella sativa (thymoquinone, TQ), as it is the major ingredient of black seed oil and extract. The treatment dose and duration were variable among studies. Combining TQ with standard PCa chemotherapeutic agents can enhance the efficacy of bone-preventive adverse events in metastatic PCa while reducing toxicity. In BPH, significant reductions in PI, prostate volume (PV) Dihydrotestosterone (DHT) levels, prostate-specific antigen (PSA), and serum malondialdehyde (MDA) were observed along with noticeable increases in serum antioxidant capacity. 4. Discussion 4.1 Traditional uses of black cumin Nigella sativa , also known as black seed or black cumin in English, Habat Al-Baraka in Arabic, and Tikur azmud in Amharic, has a long history of widespread culinary use. It has been employed as a spice and flavoring agent in a variety of dishes, including bread, yogurt, pickles, sauces, and salads. 32 This versatile seed has also held a prominent place in traditional remedies across Arabian countries, Far East Asia, Europe, and Africa, earning it the nickname “The herb from heaven” by early herbal specialists. 33 The Prophet Mohammed (PBUH) acknowledged its medicinal virtues, saying, “Hold on to the use of this black seed, as it has a remedy for every illness except death.” 34 Furthermore, Avicenna, a renowned physician from the 10th century, known for his work “The Canon of Medicine,” advocated Nigella seeds for enhancing the body’s energy and assisting recovery from exhaustion and dispiritedness. Notably, the Holy Bible mentions Nigella sativa for its therapeutic properties, and Hippocrates and Dioscorides refer to it as Melanthion. 35 , 36 Black cumin seeds have numerous medicinal applications in ancient herbal systems and are used to treat a variety of diseases. These include respiratory problems, pain treatment (such as chronic headaches and back pain), diabetes, paralysis, infections, inflammation, hypertension, and digestive system concerns, with various formulations utilized for administration. Furthermore, it has been applied topically for conditions such as blisters, nasal abscesses, orchitis, eczema, and swollen joints. 9 Considering the extensive history of traditional medicinal uses of Black cumin and their active components such as TQ, there is a compelling reason to explore this valuable herb as an effective herbal medicine with multiple pharmacological actions. Based on the published experimental studies, our review highlights the potential benefits of Black cumin for treating prostate diseases such as BPH and PCa ( Figure 4 ). Figure 4. Potential benefits of Nigella sativa seeds on human prostate based on experimental studies. 4.2 Potential efficacy of black cumin for benign prostatic hyperplasia In 2019, there were an estimated 94 million cases (95% CI 73.2 to 118 million) of BPH cases worldwide. This number marks a significant increase compared to the 51.1 million cases (95% CI 3.1 to 69.3 million) recorded in the year 2000. 37 BPH is a prevalent age-related condition of the prostate gland in men and is characterized by symptoms such as urinary tract obstruction, increased urination frequency, urinary retention, diminished urinary tube diameter, altered urine flow pressure, and post-urination dribbling. 38 This condition entails enlargement of the prostate gland due to excessive proliferation of cellular components, notably mesenchymal cells. Common therapeutic approaches encompass α-adrenergic antagonists, 5-α-reductase inhibitors, and alternative remedies with natural products. 39 Recent research has highlighted the relationship between oxidative stress (OS) and BPH. Notably, patients with BPH exhibit elevated levels of the lipid peroxidation biomarker MDA, coupled with suppressed plasma antioxidant levels. 39 , 40 This underscores the potential utility of antioxidant interventions in the management of BPH. Nonetheless, conventional treatments such as alpha-adrenergic receptor blockers and 5-alpha reductase inhibitors present side effects and economic constraints, prompting the exploration of natural compounds as lead candidates for drug development or adjunctive therapies. Investigative studies have highlighted promising alternatives and complementary options for managing mild BPH, including Serona repens, Pygeum africanum, and Secale cereals. This approach has gained traction owing to factors such as accessibility, cost-effectiveness, and comparatively superior safety profiles compared to prevailing pharmaceutical interventions. Additionally, the global trend towards harnessing natural sources for the treatment of otherwise challenging diseases has bolstered interest in botanicals and other natural reservoirs, with Nigella sativa emerging as a highly endorsed contender within this paradigm. 39 A study using the BPH rat model reported that the administration of Black cumin seed oil at doses of 00 and 800 mg/kg resulted in a discernible reduction in DHT levels. 6 Intriguingly, these findings indicated that the Black cumin oil, to a certain extent, displayed a more pronounced decrease in DHT levels within the BPH model compared to finasteride. 6 Similarly, Hiipakka et al. reported that treatment with polyphenols derived from green tea diminished DHT production and hindered prostate cell proliferation. Given Black cumin’s composition of polyphenolic compounds, 41 it stands to reason that the suppression of 5α-reductase activity potentially contributes to the beneficial impacts of this botanical. Among the fatty acids, Black cumin oil contains a substantial amount of essential unsaturated fatty acids, including approximately 1% omega-3, 25% omega-9, and 58% omega-6. 8 , 42 Prior work by Abdel-Rahman et al. posited that fatty acid-enriched compounds might impede the proliferation of prostate cells by reducing testosterone and DHT concentrations 43 This aligns with the findings of Liang et al., who demonstrated the inhibitory role of fatty acids on 5α-reductase. 42 Increased prostate weight serves as an indicative marker for diagnosing BPH, and the Prostate Index (PI) is frequently used to gauge BPH progression. 44 A study on the rat of the model reported that both 00 and 800 mg/kg doses of Black cumin seed oil significantly decreased both PI and PV in the context of BPH. 6 Recent insights have revealed the potential of PV and PSA concentrations in predicting the growth of prostate cells. Notably, PSA can serve as a surrogate index for PV and as a diagnostic marker for assessing the risk of prostate carcinoma. 44 Hence, an elevated PSA level corresponds to heightened proliferation of prostate cells. A study on the BPH rat model reported that treatment with N. sativa seed oil at doses of 00 and 800 mg/kg prominently reduced PSA concentrations compared to the BPH model control group. 6 Ren et al. highlighted the ability of polyphenols to repress PSA gene expression, 45 suggesting that the ability of N. sativa to reduce PSA levels may be attributed to the presence of polyphenols. 6 Consequently, the observed effect of N. sativa oil in hindering lipid peroxidation, and by extension, its potential anti-BPH effects, is likely attributable to its reservoir of antioxidant and free-radical-quenching compounds. A study concerning serum MDA levels, further underscored this assertion, as these parameters were notably elevated in the BPH group compared to the control group. 6 Remarkably, in this animal study, within the N. sativa oil-treated groups, a significant reduction in serum MDA levels was evident compared to the BPH group. This reduction strongly signifies the shielding effects of the constituents present in N. sativa oil, thereby potentially enhancing serum antioxidant capacity and concurrently lowering MDA levels. The observed decline in MDA levels appeared to align with the inherent antioxidant potency of plants. 6 4.3 Assessing black cumin’s anticancer properties against prostate cancer The increasing global incidence of cancer poses significant medical challenges. In response, there has been a growing endeavor to explore potent natural anticancer treatments as alternatives to existing chemotherapeutic approaches, which often have limited applicability. PCa is one of the most prevalent malignancies affecting men, 46 and recent research has unveiled the noteworthy role of TQ, a prominent bioactive compound in Nigella sativa , in influencing PCa markers ( Table 2 ). TQ, a pivotal constituent of black seed oil, has a wide spectrum of pharmacological effects including potent anti-inflammatory properties 47 and notable antioxidant activity. 48 Furthermore, TQ was the predominant bioactive compound extracted from Black cumin. Its abundance has been linked to its antineoplastic properties against a diverse array of tumors. 49 , 50 TQ has garnered attention for its antineoplastic properties in various cancers, including pancreatic cancer, 48 lung cancer, colon cancer, 51 and leukemia. 52 Research has shown that TQ not only curbs growth and triggers cell apoptosis and cell cycle arrest, but also deters metastasis and angiogenesis. These multifaceted effects are attributed to its modulation of key signaling pathways such as Akt, 53 NF-κB, 54 mitogen-activated protein kinase (MAPK), and Signal transducer and activator of transcription 3 (STAT3). 55 In this compilation, we have summarized the present scientific knowledge concerning the anticancer properties of Nigella sativa , along with elucidating its mechanism of action, with a specific focus on PCa. Findings from the study on the effect of TQ on human PCa cell lines DU15 and human prostate cancer cell line (PC3) revealed that TQ effectively curbed the metastatic attributes and restrained the process of epithelial-mesenchymal transition (EMT) within PCa cells through its active downregulation of the TGF-β/Smad2/3 signaling pathway. Furthermore, these outcomes lend support to the proposition that TQ holds promising potential as a therapeutic agent against PCa, functioning by precisely targeting the TGF-β pathway. 22 However, the relationship between the TQ and EMT in PCa remains unclear. Furthermore, the precise mechanism underlying TQs inhibition of the metastatic phenotype remains to be fully elucidated. A study explored the combination of docetaxel and TQ in hormone-refractory prostate cancer cells (DU-15) and its impact on PI3K and ERK signaling pathways tested the effect of PI3K and ERK inhibitors (LY294002 and FR 180204) cells respectively, were treated with the inhibitors for one hour, and then treated with docetaxel in combination with TQ. 23 The combination of docetaxel and TQ showed a significant increase in cytotoxic and apoptotic effects compared to using each agent separately, with the effect becoming stronger at higher doses. Interestingly, the presence of LY294002 did not substantially alter cell viability when combined with docetaxel and TQ, unlike cells treated with LY294002 alone. - However, introducing FR18020 reduced cell viability significantly when combined with docetaxel and TQ, compared to cells treated solely with the inhibitor. The study suggests that the cytotoxic effect of docetaxel and TQ is connected to the inhibition of the PI3K/Akt signaling pathway in DU-15 cells. 23 This combined approach has the potential to offer an alternative to contemporary oncological practices. Additionally, the synergistic use of docetaxel and TQ holds promise for potentially reducing the dosage of docetaxel and mitigating its associated adverse effects while maintaining therapeutic effectiveness for patients with castration-resistant prostate cancer (CRPC). 23 In an in vitro study on human prostate carcinoma LnCaP cells, TQ decreased cell viability and enhanced apoptosis by activating caspase-9. 24 TQ significantly reduces cancer cell survival through apoptosis, with its effects being time-dependent and substantial. Moreover, an investigation into the mode of action of TQ in androgen receptor (AR)-naïve (PC-3) and AR-independent (C-2B) PCa cells revealed that TQ inhibited the growth of human prostate C-2B cancer cells by inducing growth arrest, JNK activation, and DNA-damage-inducible 45 alpha (GADD45a), while also downregulating Bcl-2-related proteins, such as BAG-1, Bcl-2, Bcl2A1, Bcl2L1, and BID. 25 Moreover, TQ has the ability to inhibit growth in C-2B and PC3 cells by raising reactive oxygen species (ROS) and lowering glutathione (GST) levels in both of these cells. 25 TQ-induced cell death is primarily caused by increased ROS generation and decreased GSH levels and is not influenced by AR activity. Furthermore, TQ demonstrated a pro-oxidant cytotoxic mechanism, including oxidative DNA damage, which was enhanced through a copper-dependent pathway by mobilizing and decreasing endogenous cellular copper across multiple PCa cell lines, including DU15, LNCaP, PC3, and C2B. 26 This pro-oxidant cytotoxic pathway provides a more thorough understanding of the anticancer efficacy of plant-based antioxidants. 26 A study found that TQ, a naturally produced herbal substance, has potential as a treatment for both hormone-sensitive and hormone-refractory PCa. Furthermore, given its specific effect on cancer cells, we believe that TQ could be safely used as a preventive measure against the start of PCa. 27 TQ has potential benefits in treating hormone-sensitive and hormone-resistant prostate cancer, and its selective action on cancer cells makes it safely administered to help prevent PCa. TQ exerts inhibitory effects on the expression of AR and E2F-1, which are crucial for the proliferation and viability of androgen-sensitive and androgen-independent prostate cancer cells, both in vivo and in vitro. The efficacy of TQ is evident in its ability to diminish the levels of AR and E2F-1 while promoting the activation of pro-apoptotic proteins, including p53, p21Cip1, p27Kip1, and Bax, in androgen-sensitive prostate cancer cells. 27 TQ inhibited tumor growth in xenografts originating from androgen-independent C-2B prostate cancer cells in nude mice. Consistent with its effect on cultured cells, this outcome correlated with a substantial reduction in AR and E2F-1 expression and the initiation of apoptosis. Consequently, our perspective is that TQ holds promise as a potential therapy for PCa, particularly in hormone-refractory cases. 27 Additionally, TQ dose-dependency increased the inhibitory effect of TQ on DNA synthesis, proliferation, and viability of cancerous cells (LNCaP, C-2B, PC-3, and DU15), but not in non-cancerous prostate (BPH-1) epithelial cells. 27 Another study reported that TQ effectively blocked angiogenesis both in vitro and in vivo, 28 exhibited preventive effects on tumor angiogenesis in the PC3 mouse model, and curbed human prostate tumor growth at a low dose with minimal chemo-toxic side effects. Notably, this study observed a heightened sensitivity of endothelial cells to TQ-induced phenomena, including apoptosis, suppression of proliferation, and hindered migration, in contrast to PC3 cancer cells. Furthermore, TQ effectively restrained the activation of extracellular signal-regulated kinase induced by vascular endothelial growth factor but did not affect the activation of vascular endothelial growth factor receptor 2. 28 These findings led to the conclusion that TQ can efficiently inhibit prostate tumor growth at an early tumor stage (50 mm 3 ) at a dose of 6 mg/kg/day. 28 A study on the nanoparticle optimization of Nigella sativa reported the successful development and characterization of a nano-based carrier for Nigella sativa essential oil using optimization techniques, and a methyl thiazolyl-diphenyl-tetrazolium bromide (MTT) assay was performed to compare the in vitro cytotoxicity using two different cell lines (i.e., HCT 116 for colorectal carcinoma and PC3 for prostatic cancer). This study demonstrated the enhanced properties of nanoparticulated oil, including improved efficiency in suppressing cancer cell viability compared to free oil. 29 Another study reported that TQ can block metastatic processes induced by IL-7 in prostate cancer cells, thereby controlling tumor progression, migration, and invasion. 30 An in vitro study found that the combination of TQ and zoledronic acid (ZA) led to increased cytotoxic effects and apoptosis in prostate cancer cell lines resistant to both hormones and drugs. This novel combination approach could serve as an alternative strategy for patients with limited treatment options due to poor performance status and those who are not viable candidates for traditional therapies. In addition, compared with cytotoxic agents, it exhibits a minimal profile of hematological and non-hematological toxicity. 31 These studies suggest that Black cumin may play a role in slowing the progression of prostate cancer; however, clinical trials in humans are necessary to determine its efficacy and safety. It is important to approach these findings with caution and consult medical professionals before considering complementary or alternative treatments, particularly for serious conditions such as cancer. Limitation This review has certain limitations, including issues that may influence its quality, validity, and reliability. However, this is the first paper to provide a complete assessment of the emerging evidence and insights from in vitro and in vivo studies investigating the possible benefit of Black cumin ( Nigella sativa L. ) on prostate health and disorders such as BPH and PCa. Recommendation and future directions Suggestions and possible directions for utilizing the benefits of Black cumin ( Nigella sativa L. ) in enhancing prostate health might encourage researchers to conduct more rigorous clinical trials to validate the specific effects of Black cumin on prostate health. These studies should include varied populations, long-term assessments, and in-depth study to determine the precise processes by which black cumin chemicals interact with prostate cells and alter hormonal balance. This information will contribute to a better understanding of their possible therapeutic benefits. Furthermore, we identified the most suitable dosage and time for Black Cumin supplementation to enhance prostate health advantages. This includes looking into both short- and long-term impacts at different dosage levels. In addition, we investigated the synergistic benefits of combining black cumin with known prostate cancer treatments. This could potentially improve therapeutic success while minimizing side effects. Furthermore, we discovered and isolated the major bioactive components in Black cumin that are responsible for its beneficial benefits on prostate health. This information could lead to the creation of specialized vitamins and treatments. Continued evaluation of the safety profile of black cumin supplementation is required, particularly in the context of long-term use, as well as potential drug interactions. Future efforts should focus on improving its application through research-backed dosages and combination medicines, as well as effectively conveying its potential advantages to the general public and healthcare practitioners. 5. Conclusions Thymoquinone (TQ), a bioactive chemical found in Nigella sativa , is known to have antioxidant, anti-inflammatory, and anticancer properties on prostate tissues. Over the last decade, these effects have been studied both in vivo and in vitro. We expect that the findings of this review will be used to advance the potential treatment alternatives obtained from black cumin for human prostate health. According to the findings of our review, the TQ component of Nigella sativa has promising potential benefits for prostate health. TQ has the potential to increase pro-oxidant-induced cell death, inhibit tumor angiogenesis, induce apoptosis, and prevent metastasis in PCa experimental models. Combining TQ with standard PCa chemotherapeutic agents can enhance the efficacy of bone-preventive adverse events in metastatic PCa while reducing toxicity. Significant reductions in PI, PV, DHT, PSA, and serum MDA levels as well as significant improvements in serum antioxidant capacity have been reported in BPH experimental models. This natural product can then be utilized to treat various diseases and has become a popular functional food. 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Abdel-Rahman MK: Effect of pumpkin seed (Cucurbita pepo L.) diets on benign prostatic hyperplasia (BPH): chemical and morphometric evaluation in rats. World J Chem. 2006; 1 (1): 33–40. 44. Roehrborn CG, Boyle P, Gould AL, et al. : Serum prostate-specific antigen as a predictor of prostate volume in men with benign prostatic hyperplasia. Urology. 1999; 53 (3): 581–589. Publisher Full Text 45. Ren F, Zhang S, Mitchell SH, et al. : Tea polyphenols down-regulate the expression of the androgen receptor in LNCaP prostate cancer cells. Oncogene. 2000; 19 (15): 1924–1932. PubMed Abstract | Publisher Full Text 46. Wang L, Lu B, He M, et al. : Prostate Cancer Incidence and Mortality: Global Status and Temporal Trends in 89 Countries From 2000 to 2019. Front Public Health. 2022; 10 : 811044. Published 2022 Feb 16. PubMed Abstract | Publisher Full Text | Free Full Text 47. Hossen MJ, Yang WS, Kim D, et al. : Thymoquinone: An IRAK1 inhibitor with in vivo and in vitro anti-inflammatory activities. Sci Rep. 2017; 7 : 42995. Published 2017 Feb 20. PubMed Abstract | Publisher Full Text | Free Full Text 48. Dur A, Kose H, Kocyigit A, et al. : The anti-inflammatory and antioxidant effects of thymoquinone on ceruleine induced acute pancreatitis in rats. Bratisl Lek Listy. 2016; 117 (10): 614–618. PubMed Abstract | Publisher Full Text 49. Attoub S, Sperandio O, Raza H, et al. : Thymoquinone as an anticancer agent: evidence from inhibition of cancer cells viability and invasion in vitro and tumor growth in vivo. Fundam Clin Pharmacol. 2013; 27 (5): 557–569. PubMed Abstract | Publisher Full Text 50. Khan MA, Chen HC, Tania M, et al. : Anticancer activities of Nigella sativa (black cumin). Afr J Tradit Complement Altern Med. 2011; 8 (5 Suppl): 226–232. PubMed Abstract | Publisher Full Text | Free Full Text 51. Acharya BR, Chatterjee A, Ganguli A, et al. : Thymoquinone inhibits microtubule polymerization by tubulin binding and causes mitotic arrest following apoptosis in A549 cells. Biochimie. 2014; 97 : 78–91. PubMed Abstract | Publisher Full Text 52. Salim LZ, Othman R, Abdulla MA, et al. : Thymoquinone inhibits murine leukemia WEHI-3 cells in vivo and in vitro [published correction appears in PLoS One. 2015;10(3):e0120034]. PLoS One. 2014; 9 (12): e115340. Published 2014 Dec 22. PubMed Abstract | Publisher Full Text | Free Full Text 53. Xu D, Ma Y, Zhao B, et al. : Thymoquinone induces G2/M arrest, inactivates PI3K/Akt and nuclear factor-κB pathways in human cholangiocarcinomas both in vitro and in vivo. Oncol Rep. 2014; 31 (5): 2063–2070. PubMed Abstract | Publisher Full Text 54. Zhang L, Bai Y, Yang Y: Thymoquinone chemosensitizes colon cancer cells through inhibition of NF-κB. Oncol Lett. 2016; 12 (4): 2840–2845. PubMed Abstract | Publisher Full Text | Free Full Text 55. Woo CC, Hsu A, Kumar AP, et al. : Thymoquinone inhibits tumor growth and induces apoptosis in a breast cancer xenograft mouse model: the role of p38 MAPK and ROS. PLoS One. 2013; 8 (10): e75356. Published 2013 Oct 2. PubMed Abstract | Publisher Full Text | Free Full Text Comments on this article Comments (0) Version 2 VERSION 2 PUBLISHED 27 Mar 2024 ADD YOUR COMMENT Comment Author details Author details 1 Urology, College of Medicine, Majmaah University, Al Majmaah, Riyadh Province, 11952, Saudi Arabia 2 Urology, Faculty of Medicine, King Saud University,, Riyadh, Riyadh Province, 11461, Saudi Arabia 3 College of Medicine, Majmaah University, Al Majmaah, Riyadh Province, 11952, Saudi Arabia 4 College of Medicine, Umm Al-Qura University, Mecca, Makkah Province, 24381, Saudi Arabia 5 Urology, Prince Mansour Military Hospital, Taif, Makkah Province, 26526, Saudi Arabia 6 Basic Medical Science, Majmaah University, Al Majmaah, Riyadh Province, 11952, Saudi Arabia 7 Urology, King Fahd Hospital, Madinah, Madinah, 42210, Saudi Arabia Meshari A. Alzahrani Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Ibrahim Abunohaiah Roles: Writing – Original Draft Preparation Yousuf Altuwaijry Roles: Writing – Original Draft Preparation Muath Alahmadi Roles: Writing – Original Draft Preparation Osama Qasim Roles: Writing – Original Draft Preparation Abdulaziz Alzahrani Roles: Writing – Original Draft Preparation Shamshad Begum Loni Roles: Writing – Original Draft Preparation Mohammed Shareef Roles: Writing – Original Draft Preparation Raed Almannie Roles: Validation, Visualization, Writing – Review & Editing Saleh Binsaleh Roles: Validation, Visualization, Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Article Versions (2) version 2 Revised Published: 21 Feb 2025, 13:229 https://doi.org/10.12688/f1000research.145024.2 version 1 Published: 27 Mar 2024, 13:229 https://doi.org/10.12688/f1000research.145024.1 Copyright © 2025 Alzahrani MA et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Alzahrani MA, Abunohaiah I, Altuwaijry Y et al. Effect of Black Cumin ( Nigella sativa ) on Prostate Health: Narrative Review [version 2; peer review: 4 approved with reservations] . F1000Research 2025, 13 :229 ( https://doi.org/10.12688/f1000research.145024.2 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 2 VERSION 2 PUBLISHED 21 Feb 2025 Revised Views 0 Cite How to cite this report: Abuelezz NZ. Reviewer Report For: Effect of Black Cumin ( Nigella sativa ) on Prostate Health: Narrative Review [version 2; peer review: 4 approved with reservations] . F1000Research 2025, 13 :229 ( https://doi.org/10.5256/f1000research.173440.r393994 ) The direct URL for this report is: https://f1000research.com/articles/13-229/v2#referee-response-393994 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 08 Aug 2025 Nermeen Z Abuelezz , Misr University for Science and Technology, Giza, Egypt Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.173440.r393994 In this study, the authors discussed the therapeutic potential of black cumin seed oil and its constituents on prostate health with special focus on prostate cancer. Over all the manuscript is well written in a clear and a simple language. ... Continue reading READ ALL In this study, the authors discussed the therapeutic potential of black cumin seed oil and its constituents on prostate health with special focus on prostate cancer. Over all the manuscript is well written in a clear and a simple language. However there are some points that need to be addressed: 1- It is important to add an illustration clarifying the main mechanistic actions of TQ/black cumin constituents on biochemical parameters that contribute to prostate disorders (as inflammatory cytokines, antioxidants protective enzymes, etc,..). Together with creating a clear subtitle/subtitles in the manuscript discussing the biochemical players that are majorly impacted by black cumin seed oil in prostate disorders. 2- The vast majority of the included studies were conducted on cell lines. This is totally different from vivo studies that can be sufficient to reach a proper judgement on the actual efficacy of black cumin seed in prostate cancer. Authors are highly advised to address this point in more details in the limitations section. 3- Taking into consideration the limited numbers of studies included in this review, discussing the doses and method of administration in the cited studies were highly superficial. It is important to know and spot that black cumin seed oil contains many constituents, with thymoquinone as a the major constituent it is highly thermos and photo labile, slightly soluble in water. These factors would naturally impact the efficacy of using Back cumin seed/ constituents, However this was totally missing in the review. So i suggest this should be discussed in more details in the limitations section. 4- Also what views do the authors have regarding these limitations? This should be more highlighted in the conclusions and recommendations part. 5- In the last section, authors stated that " Furthermore, we identified the most suitable dosage and time for Black Cumin supplementation to enhance prostate health advantages." I don't think this sentence is accurate as the review only addressed in vitro studies and a very few in vivo studies on animal models. This is far from enough to determine the best dosage and interval of administration for such a claim. I highly suggest modifying this sentence to cope with the cited results. Is the topic of the review discussed comprehensively in the context of the current literature? Partly Are all factual statements correct and adequately supported by citations? Yes Is the review written in accessible language? Yes Are the conclusions drawn appropriate in the context of the current research literature? Partly Competing Interests: No competing interests were disclosed. Reviewer Expertise: Inflammation and endocrinology, molecular biology and neuroscience. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Abuelezz NZ. Reviewer Report For: Effect of Black Cumin ( Nigella sativa ) on Prostate Health: Narrative Review [version 2; peer review: 4 approved with reservations] . F1000Research 2025, 13 :229 ( https://doi.org/10.5256/f1000research.173440.r393994 ) The direct URL for this report is: https://f1000research.com/articles/13-229/v2#referee-response-393994 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Bamosa A. Reviewer Report For: Effect of Black Cumin ( Nigella sativa ) on Prostate Health: Narrative Review [version 2; peer review: 4 approved with reservations] . F1000Research 2025, 13 :229 ( https://doi.org/10.5256/f1000research.173440.r378271 ) The direct URL for this report is: https://f1000research.com/articles/13-229/v2#referee-response-378271 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 12 May 2025 Abdullah Bamosa , Imam Abdulrahman Bin Faisal University, Dammam, Eastern Province, Saudi Arabia Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.173440.r378271 Major comment: This review is covering the effect of thymoquinone on prostatic cancer and therefore I strongly recommend changing the title into (Effect of TQ on prostatic cancer) for the following reasons: 1- There ... Continue reading READ ALL Major comment: This review is covering the effect of thymoquinone on prostatic cancer and therefore I strongly recommend changing the title into (Effect of TQ on prostatic cancer) for the following reasons: 1- There is only one study related to the effect of Nigella sativa on BPH and a review article cannot be on only one study. Which means that this component of the prostate health is not covered properly in the review and cannot be part of the title. 2- The studies on prostatic cancer are all on TQ except one which is concluding that nanoparticles of Nigella sativa oil are more effective than nonencapsulated and not dealing with basic mechanisms of the anticancer effect as quoted in the article. Therefore, one article with such conclusion is not enough to make the title general for Nigella sativa. For above reasons I think the current title is not proper and should be changed as suggested above. Minor comments: Introduction: 1- Line 8 the phrase (Habit of Al-braka) omit of so it should be (Habit Albraka) 2- 4th paragraph on page 3 the astatement (in addition to TQ, black cumin seeds contain thymoquinones...) should be (in addition to TQ black cumin contain other form of quinones...) 3- On page 4, line 4, ....and promising preliminary study should be studies 4- I think better to use Nigella sativa instead of black cumin as this is the scientific name of this plant. Results: Kus (Turkey, 2018) study has been mentioned in table 1 using Nigella sativa oil while in table 2 it is stated that they have used TQ which is the right thing as shown in the title of the study. Discussion: 1- First paragraph should be shifted to the introduction and avoid repetition. 2- The paragraph on BPH should be omitted as stated in the major comment before. Recommendation: 1- In the second and third paragraphs the authors repeatedly used the phrase "we" with the past tense which is not proper and should be (we recommend to...) 2- Third paragraph, third line, (This information could lead to the creation of specialized vitamins and treatments) should be omitted. Is the topic of the review discussed comprehensively in the context of the current literature? Yes Are all factual statements correct and adequately supported by citations? Yes Is the review written in accessible language? Yes Are the conclusions drawn appropriate in the context of the current research literature? Yes Competing Interests: No competing interests were disclosed. Reviewer Expertise: Nigella sativa, diabetes mellitus I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Bamosa A. Reviewer Report For: Effect of Black Cumin ( Nigella sativa ) on Prostate Health: Narrative Review [version 2; peer review: 4 approved with reservations] . F1000Research 2025, 13 :229 ( https://doi.org/10.5256/f1000research.173440.r378271 ) The direct URL for this report is: https://f1000research.com/articles/13-229/v2#referee-response-378271 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Erdoğan Ü. Reviewer Report For: Effect of Black Cumin ( Nigella sativa ) on Prostate Health: Narrative Review [version 2; peer review: 4 approved with reservations] . F1000Research 2025, 13 :229 ( https://doi.org/10.5256/f1000research.173440.r372680 ) The direct URL for this report is: https://f1000research.com/articles/13-229/v2#referee-response-372680 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 09 Apr 2025 Ümit Erdoğan , Isparta University of Applied Sciences, Isparta, Turkey Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.173440.r372680 Comments to the author(s) I have reviewed your manuscript entitled " Effect of Black Cumin (Nigella sativa) on Prostate". Overall, the article provides comprehensive information for researchers by revealing the effects of black cumin on prostate ... Continue reading READ ALL Comments to the author(s) I have reviewed your manuscript entitled " Effect of Black Cumin (Nigella sativa) on Prostate". Overall, the article provides comprehensive information for researchers by revealing the effects of black cumin on prostate cancer. The methodology is well described. However, I suggest some minor revisions to improve clarity, accuracy, and technical details. I recommend that it be accepted for indexing after some minor changes as noted below. If the following sentences are changed in the introduction section, it will be more understandable for the reader. Recent research has highlighted black cumin’s possible influence on the prostate, sparking interest in its role in prostate-related disorders.6,9,13 “ The seeds have a high concentration of bioactive chemicals that provide numerous health benefits”….. Please provide references that contain up-to-date and detailed information. For example, the isolation of thymoquinone is given in detail in the following studies. The reference given by the authors is taken from a review and no experimental study has been done there. Erdoğan Ü et al [2024 (Ref-1)] http://dx.doi.org/10.1080/0972060X.2024.2352418 Erdoğan Ü et al [2023 (Ref-2)] http://dx.doi.org/10.1080/0972060X.2023.2176263 “Thymoquinone (TQ) (2-isopropyl-5-methyl-benzoquinone) is the main bioactive component in the volatile oil isolated from black seeds” Please use abbreviations only once throughout the text and avoid repetition Please correct "Turkey" to Turkey in the main text. For the continuation of the current research, the authors can offer recommendations in the conclusion section. As follows: Based on the authors' claim that the effects of thymoquinone on prostate cancer, molecular docking and modeling studies of thymoquinone on prostate cancer can be recommended. Is the topic of the review discussed comprehensively in the context of the current literature? Yes Are all factual statements correct and adequately supported by citations? Yes Is the review written in accessible language? Yes Are the conclusions drawn appropriate in the context of the current research literature? Partly References 1. Erdoğan Ü, Erbaş S, Muhammed M, Onem E, et al.: Isolation and characterization of thymoquinone fromNigella sativa essential oil: antioxidant and antibacterial activities, molecular modeling studies, and cytotoxic effects on lung cancer A549 cells. Journal of Essential Oil Bearing Plants . 2024; 27 (3): 787-803 Publisher Full Text 2. Erdoğan Ü, Özmen Ö, Özer M: Wound Healing, Anti-analgesic, and Antioxidant Activity ofNigella sativa Linn., Essential Based Topical Formulations in Rat Model Experimental Skin Defects. Journal of Essential Oil Bearing Plants . 2023; 26 (1): 45-60 Publisher Full Text Competing Interests: No competing interests were disclosed. Reviewer Expertise: bioactive ingredient, thymoquinone (TQ) antioxidant, anti cancer I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Erdoğan Ü. Reviewer Report For: Effect of Black Cumin ( Nigella sativa ) on Prostate Health: Narrative Review [version 2; peer review: 4 approved with reservations] . F1000Research 2025, 13 :229 ( https://doi.org/10.5256/f1000research.173440.r372680 ) The direct URL for this report is: https://f1000research.com/articles/13-229/v2#referee-response-372680 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Version 1 VERSION 1 PUBLISHED 27 Mar 2024 Views 0 Cite How to cite this report: Hull R. Reviewer Report For: Effect of Black Cumin ( Nigella sativa ) on Prostate Health: Narrative Review [version 2; peer review: 4 approved with reservations] . F1000Research 2025, 13 :229 ( https://doi.org/10.5256/f1000research.158906.r297489 ) The direct URL for this report is: https://f1000research.com/articles/13-229/v1#referee-response-297489 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 08 Aug 2024 Rodney Hull , SAMRC Precision Oncology Research Unit (PORU), DSI/NRF SARChI Chair in Precision Oncology and Cancer Prevention (POCP), Pan African Cancer Research Institute (PACRI), University of Pretoria, Pretoria, Gauteng, South Africa Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.158906.r297489 The review covers the use of black cumin ( Nigella sativa) to treat prostate ailments such as prostate cancer and Benign prostate hyperplasia. The review is generally well done and overs a topic whose review is worthwhile and would act as an ... Continue reading READ ALL The review covers the use of black cumin ( Nigella sativa) to treat prostate ailments such as prostate cancer and Benign prostate hyperplasia. The review is generally well done and overs a topic whose review is worthwhile and would act as an important resource for future studies regarding the use of this plant and its extract as a future potential therapy. However, there are a few issues with the review which need to be addressed, 1) In the abstract what s meant by the phrase functional foods- I do not hink this is the right term to use 2) In the abstract the use of the wors esteemed to describe the herb - this is not the appropriate word to use here 3) Many of the keywords used appear in the title and as such are redundant. Different keywords should be used 4) In the Methods section the authors state that they tried to avoid omission and include all pertinent information, but they also state that they removed all articles without free full text availability. while this is a practical omission it does mean that important information has been omitted based purely on the information ot being accessible. How pertinent are the omitted articles to the topic. 5) The number of total articles is incorrectly given as 2 in the text and should be 24 6) The title of table 1 is confusing and not correctly written 7) In table 1 should vitro not be in vitro 8)In results the sentence ending experimental in vivo and in vitro, sounds incomplete. 9) The authors state that most studies were from Turkey and Asia. Why are they classing Turkey as solely Asia and not Europe 10) When describing the different studies and methods the phrase "were variants" is incorrect and should be described as being variable. 11) The phrase bone-preventive adverse when referring to bone metastasus should be preventing adverse effects in bine or something similar 12) In table 2 the major findings for the Kaseb study are written wih dash type bullets which is dfferent to the other entries 13) In the discussion the use of the phrase compelling opportunity is not correct. The word oppurtunity should be replaced with words such as reason or motivation 14) Under the potential efficacy section is the 9,0 million figure give initially correct? It appears to be too low or the second figure of 51.1 million is too high 15)Should BPH rate model be rat model 16)Many treatments and compounds such as LY29002 did are used without any introduction or explaination 17) In the paragraph beginning in an in vitro study of human prostate cancer TQ is introduced again "that TQ, a naturally derived herbal product" which is redundant. This also gives the feeling that the different studies are merely being summarized independently and the results of these studies are not being integrated and discussed as a whole. If these issues are addressed I fully recommend that the paper be accepted and indexed. Is the topic of the review discussed comprehensively in the context of the current literature? Yes Are all factual statements correct and adequately supported by citations? Yes Is the review written in accessible language? Partly Are the conclusions drawn appropriate in the context of the current research literature? Partly Competing Interests: No competing interests were disclosed. Reviewer Expertise: Cancer cell biology, multi-omic profiles of cancers specific to different populations. The effect of various compounds on transcriptome ad spliceosome profiles I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Hull R. Reviewer Report For: Effect of Black Cumin ( Nigella sativa ) on Prostate Health: Narrative Review [version 2; peer review: 4 approved with reservations] . F1000Research 2025, 13 :229 ( https://doi.org/10.5256/f1000research.158906.r297489 ) The direct URL for this report is: https://f1000research.com/articles/13-229/v1#referee-response-297489 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 21 Feb 2025 Meshari Alzahrani , Urology, College of Medicine, Majmaah University, Al Majmaah, 11952, Saudi Arabia 21 Feb 2025 Author Response The review covers the use of black cumin ( Nigella sativa) to treat prostate ailments such as prostate cancer and Benign prostate hyperplasia. The review is generally well done and overs a ... Continue reading The review covers the use of black cumin ( Nigella sativa) to treat prostate ailments such as prostate cancer and Benign prostate hyperplasia. The review is generally well done and overs a topic whose review is worthwhile and would act as an important resource for future studies regarding the use of this plant and its extract as a future potential therapy. However, there are a few issues with the review which need to be addressed, Response: We would like to thank the reviewer for his valuable feedback and comments; we replay the reviewer's comments point by point and hope we meet the expectations. 1) In the abstract what s meant by the phrase functional foods- I do not think this is the right term to use Response: We change “functional food” to nutrient-rich food. 2) In the abstract the use of the wors esteemed to describe the herb - this is not the appropriate word to use here Response: We changed “esteemed to “traditional.” 3) Many of the keywords used appear in the title and as such are redundant. Different keywords should be used Response: We changed the keywords to the following: Black seed, Thymoquinone, Prostate, Benign prostatic hyperplasia, and Prostate cancer. 4) In the Methods section the authors state that they tried to avoid omission and include all pertinent information, but they also state that they removed all articles without free full text availability. while this is a practical omission it does mean that important information has been omitted based purely on the information ot being accessible. How pertinent are the omitted articles to the topic. Response: We meant abstract-only articles, so we deleted the line “ articles without full-text availability ” to avoid misunderstanding. 5) The number of total articles is incorrectly given as 2 in the text and should be 24 Response: corrected to 24 articles 6) The title of table 1 is confusing and not correctly written Response: We change the title of Table 1 to: Subject characteristics treated with black cumin (Nigella sativa). 7) In table 1 should vitro not be in vitro Response: We change. Accordingly; we keep all (vitro, vivo) without “in.” 8)In results the sentence ending experimental in vivo and in vitro, sounds incomplete. Response: We remove the line “ in vivo and in vitro ” to avoid misunderstanding 9) The authors state that most studies were from Turkey and Asia. Why are they classing Turkey as solely Asia and not Europe Response: We changed the line for more clarity to this line; “Table 1 shows the reported articles from a different continent” 10) When describing the different studies and methods the phrase "were variants" is incorrect and should be described as being variable. Response: We change the phrase “variants” to “ variable ”. 11) The phrase bone-preventive adverse when referring to bone metastasus should be preventing adverse effects in bine or something similar Response: We removed the word “bone ” to avoid misunderstanding. We agree that PCa most commonly metastasizes to the bone. However, it can also metastasize to other organs. The phrase “bone” was mentioned twice in the manuscript and was deleted. 12) In table 2 the major findings for the Kaseb study are written with dash type bullets which is different to the other entries Response: We added dash-type bullets to the remaining studies. 13) In the discussion the use of the phrase compelling opportunity is not correct. The word opportunity should be replaced with words such as reason or motivation Response: We change the phrase “opportunity” to “ reason ”. 14) Under the potential efficacy section is the 9,0 million figure give initially correct? It appears to be too low or the second figure of 51.1 million is too high Response: We revised the reference number [37] again and corrected it to 94·0 million. 15)Should BPH rate model be rat model Response: “The phrase “rate” has been changed to “ rat ” in the whole manuscript. 16)Many treatments and compounds such as LY29002 did are used without any introduction or explanation Response: We added further details about those assays used to test the efficacy of TQ on DU-145 cells. The line we added for more explanation “ tested the effect of PI3K and ERK inhibitors (LY294002 and FR 180204) cells, respectively, were treated with the inhibitors for 1 h, and then treated with docetaxel in combination with TQ.” 17) In the paragraph beginning in an in vitro study of human prostate cancer TQ is introduced again "that TQ, a naturally derived herbal product" which is redundant. This also gives the feeling that the different studies are merely being summarized independently and the results of these studies are not being integrated and discussed as a whole. Response: We added further lines for discussion to link between studies' in the discussion section. The review covers the use of black cumin ( Nigella sativa) to treat prostate ailments such as prostate cancer and Benign prostate hyperplasia. The review is generally well done and overs a topic whose review is worthwhile and would act as an important resource for future studies regarding the use of this plant and its extract as a future potential therapy. However, there are a few issues with the review which need to be addressed, Response: We would like to thank the reviewer for his valuable feedback and comments; we replay the reviewer's comments point by point and hope we meet the expectations. 1) In the abstract what s meant by the phrase functional foods- I do not think this is the right term to use Response: We change “functional food” to nutrient-rich food. 2) In the abstract the use of the wors esteemed to describe the herb - this is not the appropriate word to use here Response: We changed “esteemed to “traditional.” 3) Many of the keywords used appear in the title and as such are redundant. Different keywords should be used Response: We changed the keywords to the following: Black seed, Thymoquinone, Prostate, Benign prostatic hyperplasia, and Prostate cancer. 4) In the Methods section the authors state that they tried to avoid omission and include all pertinent information, but they also state that they removed all articles without free full text availability. while this is a practical omission it does mean that important information has been omitted based purely on the information ot being accessible. How pertinent are the omitted articles to the topic. Response: We meant abstract-only articles, so we deleted the line “ articles without full-text availability ” to avoid misunderstanding. 5) The number of total articles is incorrectly given as 2 in the text and should be 24 Response: corrected to 24 articles 6) The title of table 1 is confusing and not correctly written Response: We change the title of Table 1 to: Subject characteristics treated with black cumin (Nigella sativa). 7) In table 1 should vitro not be in vitro Response: We change. Accordingly; we keep all (vitro, vivo) without “in.” 8)In results the sentence ending experimental in vivo and in vitro, sounds incomplete. Response: We remove the line “ in vivo and in vitro ” to avoid misunderstanding 9) The authors state that most studies were from Turkey and Asia. Why are they classing Turkey as solely Asia and not Europe Response: We changed the line for more clarity to this line; “Table 1 shows the reported articles from a different continent” 10) When describing the different studies and methods the phrase "were variants" is incorrect and should be described as being variable. Response: We change the phrase “variants” to “ variable ”. 11) The phrase bone-preventive adverse when referring to bone metastasus should be preventing adverse effects in bine or something similar Response: We removed the word “bone ” to avoid misunderstanding. We agree that PCa most commonly metastasizes to the bone. However, it can also metastasize to other organs. The phrase “bone” was mentioned twice in the manuscript and was deleted. 12) In table 2 the major findings for the Kaseb study are written with dash type bullets which is different to the other entries Response: We added dash-type bullets to the remaining studies. 13) In the discussion the use of the phrase compelling opportunity is not correct. The word opportunity should be replaced with words such as reason or motivation Response: We change the phrase “opportunity” to “ reason ”. 14) Under the potential efficacy section is the 9,0 million figure give initially correct? It appears to be too low or the second figure of 51.1 million is too high Response: We revised the reference number [37] again and corrected it to 94·0 million. 15)Should BPH rate model be rat model Response: “The phrase “rate” has been changed to “ rat ” in the whole manuscript. 16)Many treatments and compounds such as LY29002 did are used without any introduction or explanation Response: We added further details about those assays used to test the efficacy of TQ on DU-145 cells. The line we added for more explanation “ tested the effect of PI3K and ERK inhibitors (LY294002 and FR 180204) cells, respectively, were treated with the inhibitors for 1 h, and then treated with docetaxel in combination with TQ.” 17) In the paragraph beginning in an in vitro study of human prostate cancer TQ is introduced again "that TQ, a naturally derived herbal product" which is redundant. This also gives the feeling that the different studies are merely being summarized independently and the results of these studies are not being integrated and discussed as a whole. Response: We added further lines for discussion to link between studies' in the discussion section. Competing Interests: No competing interests to disclose. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 21 Feb 2025 Meshari Alzahrani , Urology, College of Medicine, Majmaah University, Al Majmaah, 11952, Saudi Arabia 21 Feb 2025 Author Response The review covers the use of black cumin ( Nigella sativa) to treat prostate ailments such as prostate cancer and Benign prostate hyperplasia. The review is generally well done and overs a ... Continue reading The review covers the use of black cumin ( Nigella sativa) to treat prostate ailments such as prostate cancer and Benign prostate hyperplasia. The review is generally well done and overs a topic whose review is worthwhile and would act as an important resource for future studies regarding the use of this plant and its extract as a future potential therapy. However, there are a few issues with the review which need to be addressed, Response: We would like to thank the reviewer for his valuable feedback and comments; we replay the reviewer's comments point by point and hope we meet the expectations. 1) In the abstract what s meant by the phrase functional foods- I do not think this is the right term to use Response: We change “functional food” to nutrient-rich food. 2) In the abstract the use of the wors esteemed to describe the herb - this is not the appropriate word to use here Response: We changed “esteemed to “traditional.” 3) Many of the keywords used appear in the title and as such are redundant. Different keywords should be used Response: We changed the keywords to the following: Black seed, Thymoquinone, Prostate, Benign prostatic hyperplasia, and Prostate cancer. 4) In the Methods section the authors state that they tried to avoid omission and include all pertinent information, but they also state that they removed all articles without free full text availability. while this is a practical omission it does mean that important information has been omitted based purely on the information ot being accessible. How pertinent are the omitted articles to the topic. Response: We meant abstract-only articles, so we deleted the line “ articles without full-text availability ” to avoid misunderstanding. 5) The number of total articles is incorrectly given as 2 in the text and should be 24 Response: corrected to 24 articles 6) The title of table 1 is confusing and not correctly written Response: We change the title of Table 1 to: Subject characteristics treated with black cumin (Nigella sativa). 7) In table 1 should vitro not be in vitro Response: We change. Accordingly; we keep all (vitro, vivo) without “in.” 8)In results the sentence ending experimental in vivo and in vitro, sounds incomplete. Response: We remove the line “ in vivo and in vitro ” to avoid misunderstanding 9) The authors state that most studies were from Turkey and Asia. Why are they classing Turkey as solely Asia and not Europe Response: We changed the line for more clarity to this line; “Table 1 shows the reported articles from a different continent” 10) When describing the different studies and methods the phrase "were variants" is incorrect and should be described as being variable. Response: We change the phrase “variants” to “ variable ”. 11) The phrase bone-preventive adverse when referring to bone metastasus should be preventing adverse effects in bine or something similar Response: We removed the word “bone ” to avoid misunderstanding. We agree that PCa most commonly metastasizes to the bone. However, it can also metastasize to other organs. The phrase “bone” was mentioned twice in the manuscript and was deleted. 12) In table 2 the major findings for the Kaseb study are written with dash type bullets which is different to the other entries Response: We added dash-type bullets to the remaining studies. 13) In the discussion the use of the phrase compelling opportunity is not correct. The word opportunity should be replaced with words such as reason or motivation Response: We change the phrase “opportunity” to “ reason ”. 14) Under the potential efficacy section is the 9,0 million figure give initially correct? It appears to be too low or the second figure of 51.1 million is too high Response: We revised the reference number [37] again and corrected it to 94·0 million. 15)Should BPH rate model be rat model Response: “The phrase “rate” has been changed to “ rat ” in the whole manuscript. 16)Many treatments and compounds such as LY29002 did are used without any introduction or explanation Response: We added further details about those assays used to test the efficacy of TQ on DU-145 cells. The line we added for more explanation “ tested the effect of PI3K and ERK inhibitors (LY294002 and FR 180204) cells, respectively, were treated with the inhibitors for 1 h, and then treated with docetaxel in combination with TQ.” 17) In the paragraph beginning in an in vitro study of human prostate cancer TQ is introduced again "that TQ, a naturally derived herbal product" which is redundant. This also gives the feeling that the different studies are merely being summarized independently and the results of these studies are not being integrated and discussed as a whole. Response: We added further lines for discussion to link between studies' in the discussion section. The review covers the use of black cumin ( Nigella sativa) to treat prostate ailments such as prostate cancer and Benign prostate hyperplasia. The review is generally well done and overs a topic whose review is worthwhile and would act as an important resource for future studies regarding the use of this plant and its extract as a future potential therapy. However, there are a few issues with the review which need to be addressed, Response: We would like to thank the reviewer for his valuable feedback and comments; we replay the reviewer's comments point by point and hope we meet the expectations. 1) In the abstract what s meant by the phrase functional foods- I do not think this is the right term to use Response: We change “functional food” to nutrient-rich food. 2) In the abstract the use of the wors esteemed to describe the herb - this is not the appropriate word to use here Response: We changed “esteemed to “traditional.” 3) Many of the keywords used appear in the title and as such are redundant. Different keywords should be used Response: We changed the keywords to the following: Black seed, Thymoquinone, Prostate, Benign prostatic hyperplasia, and Prostate cancer. 4) In the Methods section the authors state that they tried to avoid omission and include all pertinent information, but they also state that they removed all articles without free full text availability. while this is a practical omission it does mean that important information has been omitted based purely on the information ot being accessible. How pertinent are the omitted articles to the topic. Response: We meant abstract-only articles, so we deleted the line “ articles without full-text availability ” to avoid misunderstanding. 5) The number of total articles is incorrectly given as 2 in the text and should be 24 Response: corrected to 24 articles 6) The title of table 1 is confusing and not correctly written Response: We change the title of Table 1 to: Subject characteristics treated with black cumin (Nigella sativa). 7) In table 1 should vitro not be in vitro Response: We change. Accordingly; we keep all (vitro, vivo) without “in.” 8)In results the sentence ending experimental in vivo and in vitro, sounds incomplete. Response: We remove the line “ in vivo and in vitro ” to avoid misunderstanding 9) The authors state that most studies were from Turkey and Asia. Why are they classing Turkey as solely Asia and not Europe Response: We changed the line for more clarity to this line; “Table 1 shows the reported articles from a different continent” 10) When describing the different studies and methods the phrase "were variants" is incorrect and should be described as being variable. Response: We change the phrase “variants” to “ variable ”. 11) The phrase bone-preventive adverse when referring to bone metastasus should be preventing adverse effects in bine or something similar Response: We removed the word “bone ” to avoid misunderstanding. We agree that PCa most commonly metastasizes to the bone. However, it can also metastasize to other organs. The phrase “bone” was mentioned twice in the manuscript and was deleted. 12) In table 2 the major findings for the Kaseb study are written with dash type bullets which is different to the other entries Response: We added dash-type bullets to the remaining studies. 13) In the discussion the use of the phrase compelling opportunity is not correct. The word opportunity should be replaced with words such as reason or motivation Response: We change the phrase “opportunity” to “ reason ”. 14) Under the potential efficacy section is the 9,0 million figure give initially correct? It appears to be too low or the second figure of 51.1 million is too high Response: We revised the reference number [37] again and corrected it to 94·0 million. 15)Should BPH rate model be rat model Response: “The phrase “rate” has been changed to “ rat ” in the whole manuscript. 16)Many treatments and compounds such as LY29002 did are used without any introduction or explanation Response: We added further details about those assays used to test the efficacy of TQ on DU-145 cells. The line we added for more explanation “ tested the effect of PI3K and ERK inhibitors (LY294002 and FR 180204) cells, respectively, were treated with the inhibitors for 1 h, and then treated with docetaxel in combination with TQ.” 17) In the paragraph beginning in an in vitro study of human prostate cancer TQ is introduced again "that TQ, a naturally derived herbal product" which is redundant. This also gives the feeling that the different studies are merely being summarized independently and the results of these studies are not being integrated and discussed as a whole. Response: We added further lines for discussion to link between studies' in the discussion section. Competing Interests: No competing interests to disclose. Close Report a concern COMMENT ON THIS REPORT Comments on this article Comments (0) Version 2 VERSION 2 PUBLISHED 27 Mar 2024 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 3 4 Version 2 (revision) 21 Feb 25 read read read Version 1 27 Mar 24 read Rodney Hull , University of Pretoria, Pretoria, South Africa Ümit Erdoğan , Isparta University of Applied Sciences, Isparta, Turkey Abdullah Bamosa , Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia Nermeen Z Abuelezz , Misr University for Science and Technology, Giza, Egypt Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Abuelezz N. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 08 Aug 2025 | for Version 2 Nermeen Z Abuelezz , Misr University for Science and Technology, Giza, Egypt 0 Views copyright © 2025 Abuelezz N. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions In this study, the authors discussed the therapeutic potential of black cumin seed oil and its constituents on prostate health with special focus on prostate cancer. Over all the manuscript is well written in a clear and a simple language. However there are some points that need to be addressed: 1- It is important to add an illustration clarifying the main mechanistic actions of TQ/black cumin constituents on biochemical parameters that contribute to prostate disorders (as inflammatory cytokines, antioxidants protective enzymes, etc,..). Together with creating a clear subtitle/subtitles in the manuscript discussing the biochemical players that are majorly impacted by black cumin seed oil in prostate disorders. 2- The vast majority of the included studies were conducted on cell lines. This is totally different from vivo studies that can be sufficient to reach a proper judgement on the actual efficacy of black cumin seed in prostate cancer. Authors are highly advised to address this point in more details in the limitations section. 3- Taking into consideration the limited numbers of studies included in this review, discussing the doses and method of administration in the cited studies were highly superficial. It is important to know and spot that black cumin seed oil contains many constituents, with thymoquinone as a the major constituent it is highly thermos and photo labile, slightly soluble in water. These factors would naturally impact the efficacy of using Back cumin seed/ constituents, However this was totally missing in the review. So i suggest this should be discussed in more details in the limitations section. 4- Also what views do the authors have regarding these limitations? This should be more highlighted in the conclusions and recommendations part. 5- In the last section, authors stated that " Furthermore, we identified the most suitable dosage and time for Black Cumin supplementation to enhance prostate health advantages." I don't think this sentence is accurate as the review only addressed in vitro studies and a very few in vivo studies on animal models. This is far from enough to determine the best dosage and interval of administration for such a claim. I highly suggest modifying this sentence to cope with the cited results. Is the topic of the review discussed comprehensively in the context of the current literature? Partly Are all factual statements correct and adequately supported by citations? Yes Is the review written in accessible language? Yes Are the conclusions drawn appropriate in the context of the current research literature? Partly Competing Interests No competing interests were disclosed. Reviewer Expertise Inflammation and endocrinology, molecular biology and neuroscience. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (0) Abuelezz NZ. Peer Review Report For: Effect of Black Cumin ( Nigella sativa ) on Prostate Health: Narrative Review [version 2; peer review: 4 approved with reservations] . F1000Research 2025, 13 :229 ( https://doi.org/10.5256/f1000research.173440.r393994) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/13-229/v2#referee-response-393994 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Bamosa A. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 12 May 2025 | for Version 2 Abdullah Bamosa , Imam Abdulrahman Bin Faisal University, Dammam, Eastern Province, Saudi Arabia 0 Views copyright © 2025 Bamosa A. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Major comment: This review is covering the effect of thymoquinone on prostatic cancer and therefore I strongly recommend changing the title into (Effect of TQ on prostatic cancer) for the following reasons: 1- There is only one study related to the effect of Nigella sativa on BPH and a review article cannot be on only one study. Which means that this component of the prostate health is not covered properly in the review and cannot be part of the title. 2- The studies on prostatic cancer are all on TQ except one which is concluding that nanoparticles of Nigella sativa oil are more effective than nonencapsulated and not dealing with basic mechanisms of the anticancer effect as quoted in the article. Therefore, one article with such conclusion is not enough to make the title general for Nigella sativa. For above reasons I think the current title is not proper and should be changed as suggested above. Minor comments: Introduction: 1- Line 8 the phrase (Habit of Al-braka) omit of so it should be (Habit Albraka) 2- 4th paragraph on page 3 the astatement (in addition to TQ, black cumin seeds contain thymoquinones...) should be (in addition to TQ black cumin contain other form of quinones...) 3- On page 4, line 4, ....and promising preliminary study should be studies 4- I think better to use Nigella sativa instead of black cumin as this is the scientific name of this plant. Results: Kus (Turkey, 2018) study has been mentioned in table 1 using Nigella sativa oil while in table 2 it is stated that they have used TQ which is the right thing as shown in the title of the study. Discussion: 1- First paragraph should be shifted to the introduction and avoid repetition. 2- The paragraph on BPH should be omitted as stated in the major comment before. Recommendation: 1- In the second and third paragraphs the authors repeatedly used the phrase "we" with the past tense which is not proper and should be (we recommend to...) 2- Third paragraph, third line, (This information could lead to the creation of specialized vitamins and treatments) should be omitted. Is the topic of the review discussed comprehensively in the context of the current literature? Yes Are all factual statements correct and adequately supported by citations? Yes Is the review written in accessible language? Yes Are the conclusions drawn appropriate in the context of the current research literature? Yes Competing Interests No competing interests were disclosed. Reviewer Expertise Nigella sativa, diabetes mellitus I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (0) Bamosa A. Peer Review Report For: Effect of Black Cumin ( Nigella sativa ) on Prostate Health: Narrative Review [version 2; peer review: 4 approved with reservations] . F1000Research 2025, 13 :229 ( https://doi.org/10.5256/f1000research.173440.r378271) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/13-229/v2#referee-response-378271 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Erdoğan Ü. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 09 Apr 2025 | for Version 2 Ümit Erdoğan , Isparta University of Applied Sciences, Isparta, Turkey 0 Views copyright © 2025 Erdoğan Ü. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Comments to the author(s) I have reviewed your manuscript entitled " Effect of Black Cumin (Nigella sativa) on Prostate". Overall, the article provides comprehensive information for researchers by revealing the effects of black cumin on prostate cancer. The methodology is well described. However, I suggest some minor revisions to improve clarity, accuracy, and technical details. I recommend that it be accepted for indexing after some minor changes as noted below. If the following sentences are changed in the introduction section, it will be more understandable for the reader. Recent research has highlighted black cumin’s possible influence on the prostate, sparking interest in its role in prostate-related disorders.6,9,13 “ The seeds have a high concentration of bioactive chemicals that provide numerous health benefits”….. Please provide references that contain up-to-date and detailed information. For example, the isolation of thymoquinone is given in detail in the following studies. The reference given by the authors is taken from a review and no experimental study has been done there. Erdoğan Ü et al [2024 (Ref-1)] http://dx.doi.org/10.1080/0972060X.2024.2352418 Erdoğan Ü et al [2023 (Ref-2)] http://dx.doi.org/10.1080/0972060X.2023.2176263 “Thymoquinone (TQ) (2-isopropyl-5-methyl-benzoquinone) is the main bioactive component in the volatile oil isolated from black seeds” Please use abbreviations only once throughout the text and avoid repetition Please correct "Turkey" to Turkey in the main text. For the continuation of the current research, the authors can offer recommendations in the conclusion section. As follows: Based on the authors' claim that the effects of thymoquinone on prostate cancer, molecular docking and modeling studies of thymoquinone on prostate cancer can be recommended. Is the topic of the review discussed comprehensively in the context of the current literature? Yes Are all factual statements correct and adequately supported by citations? Yes Is the review written in accessible language? Yes Are the conclusions drawn appropriate in the context of the current research literature? Partly References 1. Erdoğan Ü, Erbaş S, Muhammed M, Onem E, et al.: Isolation and characterization of thymoquinone fromNigella sativa essential oil: antioxidant and antibacterial activities, molecular modeling studies, and cytotoxic effects on lung cancer A549 cells. Journal of Essential Oil Bearing Plants . 2024; 27 (3): 787-803 Publisher Full Text 2. Erdoğan Ü, Özmen Ö, Özer M: Wound Healing, Anti-analgesic, and Antioxidant Activity ofNigella sativa Linn., Essential Based Topical Formulations in Rat Model Experimental Skin Defects. Journal of Essential Oil Bearing Plants . 2023; 26 (1): 45-60 Publisher Full Text Competing Interests No competing interests were disclosed. Reviewer Expertise bioactive ingredient, thymoquinone (TQ) antioxidant, anti cancer I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (0) Erdoğan Ü. Peer Review Report For: Effect of Black Cumin ( Nigella sativa ) on Prostate Health: Narrative Review [version 2; peer review: 4 approved with reservations] . F1000Research 2025, 13 :229 ( https://doi.org/10.5256/f1000research.173440.r372680) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/13-229/v2#referee-response-372680 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2024 Hull R. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 08 Aug 2024 | for Version 1 Rodney Hull , SAMRC Precision Oncology Research Unit (PORU), DSI/NRF SARChI Chair in Precision Oncology and Cancer Prevention (POCP), Pan African Cancer Research Institute (PACRI), University of Pretoria, Pretoria, Gauteng, South Africa 0 Views copyright © 2024 Hull R. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions The review covers the use of black cumin ( Nigella sativa) to treat prostate ailments such as prostate cancer and Benign prostate hyperplasia. The review is generally well done and overs a topic whose review is worthwhile and would act as an important resource for future studies regarding the use of this plant and its extract as a future potential therapy. However, there are a few issues with the review which need to be addressed, 1) In the abstract what s meant by the phrase functional foods- I do not hink this is the right term to use 2) In the abstract the use of the wors esteemed to describe the herb - this is not the appropriate word to use here 3) Many of the keywords used appear in the title and as such are redundant. Different keywords should be used 4) In the Methods section the authors state that they tried to avoid omission and include all pertinent information, but they also state that they removed all articles without free full text availability. while this is a practical omission it does mean that important information has been omitted based purely on the information ot being accessible. How pertinent are the omitted articles to the topic. 5) The number of total articles is incorrectly given as 2 in the text and should be 24 6) The title of table 1 is confusing and not correctly written 7) In table 1 should vitro not be in vitro 8)In results the sentence ending experimental in vivo and in vitro, sounds incomplete. 9) The authors state that most studies were from Turkey and Asia. Why are they classing Turkey as solely Asia and not Europe 10) When describing the different studies and methods the phrase "were variants" is incorrect and should be described as being variable. 11) The phrase bone-preventive adverse when referring to bone metastasus should be preventing adverse effects in bine or something similar 12) In table 2 the major findings for the Kaseb study are written wih dash type bullets which is dfferent to the other entries 13) In the discussion the use of the phrase compelling opportunity is not correct. The word oppurtunity should be replaced with words such as reason or motivation 14) Under the potential efficacy section is the 9,0 million figure give initially correct? It appears to be too low or the second figure of 51.1 million is too high 15)Should BPH rate model be rat model 16)Many treatments and compounds such as LY29002 did are used without any introduction or explaination 17) In the paragraph beginning in an in vitro study of human prostate cancer TQ is introduced again "that TQ, a naturally derived herbal product" which is redundant. This also gives the feeling that the different studies are merely being summarized independently and the results of these studies are not being integrated and discussed as a whole. If these issues are addressed I fully recommend that the paper be accepted and indexed. Is the topic of the review discussed comprehensively in the context of the current literature? Yes Are all factual statements correct and adequately supported by citations? Yes Is the review written in accessible language? Partly Are the conclusions drawn appropriate in the context of the current research literature? Partly Competing Interests No competing interests were disclosed. Reviewer Expertise Cancer cell biology, multi-omic profiles of cancers specific to different populations. The effect of various compounds on transcriptome ad spliceosome profiles I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 21 Feb 2025 Meshari Alzahrani, Urology, College of Medicine, Majmaah University, Al Majmaah, 11952, Saudi Arabia The review covers the use of black cumin ( Nigella sativa) to treat prostate ailments such as prostate cancer and Benign prostate hyperplasia. The review is generally well done and overs a topic whose review is worthwhile and would act as an important resource for future studies regarding the use of this plant and its extract as a future potential therapy. However, there are a few issues with the review which need to be addressed, Response: We would like to thank the reviewer for his valuable feedback and comments; we replay the reviewer's comments point by point and hope we meet the expectations. 1) In the abstract what s meant by the phrase functional foods- I do not think this is the right term to use Response: We change “functional food” to nutrient-rich food. 2) In the abstract the use of the wors esteemed to describe the herb - this is not the appropriate word to use here Response: We changed “esteemed to “traditional.” 3) Many of the keywords used appear in the title and as such are redundant. Different keywords should be used Response: We changed the keywords to the following: Black seed, Thymoquinone, Prostate, Benign prostatic hyperplasia, and Prostate cancer. 4) In the Methods section the authors state that they tried to avoid omission and include all pertinent information, but they also state that they removed all articles without free full text availability. while this is a practical omission it does mean that important information has been omitted based purely on the information ot being accessible. How pertinent are the omitted articles to the topic. Response: We meant abstract-only articles, so we deleted the line “ articles without full-text availability ” to avoid misunderstanding. 5) The number of total articles is incorrectly given as 2 in the text and should be 24 Response: corrected to 24 articles 6) The title of table 1 is confusing and not correctly written Response: We change the title of Table 1 to: Subject characteristics treated with black cumin (Nigella sativa). 7) In table 1 should vitro not be in vitro Response: We change. Accordingly; we keep all (vitro, vivo) without “in.” 8)In results the sentence ending experimental in vivo and in vitro, sounds incomplete. Response: We remove the line “ in vivo and in vitro ” to avoid misunderstanding 9) The authors state that most studies were from Turkey and Asia. Why are they classing Turkey as solely Asia and not Europe Response: We changed the line for more clarity to this line; “Table 1 shows the reported articles from a different continent” 10) When describing the different studies and methods the phrase "were variants" is incorrect and should be described as being variable. Response: We change the phrase “variants” to “ variable ”. 11) The phrase bone-preventive adverse when referring to bone metastasus should be preventing adverse effects in bine or something similar Response: We removed the word “bone ” to avoid misunderstanding. We agree that PCa most commonly metastasizes to the bone. However, it can also metastasize to other organs. The phrase “bone” was mentioned twice in the manuscript and was deleted. 12) In table 2 the major findings for the Kaseb study are written with dash type bullets which is different to the other entries Response: We added dash-type bullets to the remaining studies. 13) In the discussion the use of the phrase compelling opportunity is not correct. The word opportunity should be replaced with words such as reason or motivation Response: We change the phrase “opportunity” to “ reason ”. 14) Under the potential efficacy section is the 9,0 million figure give initially correct? It appears to be too low or the second figure of 51.1 million is too high Response: We revised the reference number [37] again and corrected it to 94·0 million. 15)Should BPH rate model be rat model Response: “The phrase “rate” has been changed to “ rat ” in the whole manuscript. 16)Many treatments and compounds such as LY29002 did are used without any introduction or explanation Response: We added further details about those assays used to test the efficacy of TQ on DU-145 cells. The line we added for more explanation “ tested the effect of PI3K and ERK inhibitors (LY294002 and FR 180204) cells, respectively, were treated with the inhibitors for 1 h, and then treated with docetaxel in combination with TQ.” 17) In the paragraph beginning in an in vitro study of human prostate cancer TQ is introduced again "that TQ, a naturally derived herbal product" which is redundant. This also gives the feeling that the different studies are merely being summarized independently and the results of these studies are not being integrated and discussed as a whole. Response: We added further lines for discussion to link between studies' in the discussion section. View more View less Competing Interests No competing interests to disclose. reply Respond Report a concern Hull R. Peer Review Report For: Effect of Black Cumin ( Nigella sativa ) on Prostate Health: Narrative Review [version 2; peer review: 4 approved with reservations] . F1000Research 2025, 13 :229 ( https://doi.org/10.5256/f1000research.158906.r297489) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. 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