Phytochemistry, Bioavailability, and Molecular Mechanisms Underlying Multitarget Anticancer Activity of Aloe vera

Comment No.

Reviewer Comment

Authors' Response

General

The manuscript entitled “Phytochemistry, Bioavailability, and Molecular Mechanisms underlying multitarget anticancer activity of Aloe vera” by Haroon et al reviewed the anti-cancer action of Aloe vera and its bioactive compounds in various cancers. The study aimed to investigate various cancer signaling pathways targeted by Aloe vera and its bioactive compounds across different types of cancer. The review highlights that Aloe vera and its bioactive constituents show promise as multi-target anticancer agents.  Exploring the anticancer potential of natural products is valuable, as they may exert individual effects or act synergistically in combination with chemotherapy and radiation therapy. This review compiles and documents not only the anticancer effects of whole Aloe vera extracts and gel but also identifies and describes the individual actions of the bioactive compounds present in the plant. The authors have clearly described the sources used to collect relevant reports, as well as the keywords applied in the search process. However, inclusion of more available reports would enhance the overall clarity of the manuscript.

We thank the reviewer for the positive and constructive evaluation of our manuscript. We appreciate the recognition of the relevance of Aloe vera and its bioactive compounds as multitarget anticancer agents. The manuscript has been revised carefully to improve clarity, strengthen the evidence base, and address all specific comments raised by the reviewer.

1

Page 3, Materials & Method section: the authors mentioned the review prepared using “Literature published during the specific timeframe of 2019 - 2025”.  It may be better to go back few more years to collect the literature to collect most of the valuable information on this topic.

Thank you for this helpful suggestion. We have revised the Materials and Methods section by expanding the search period to include relevant earlier studies where necessary. This allowed us to include foundational and high-value reports on Aloe vera phytochemistry, bioavailability, anticancer mechanisms, and toxicity that were published before 2019. The revised methods now explain that recent studies were prioritized while older seminal studies were included when they provided essential mechanistic or experimental evidence.

2

The authors have provided a detailed explanation of the effects of Aloe vera on various solid cancers. However, substantial information is also available regarding its impact on different types of leukemia, and it would be beneficial to include relevant reports on these aspects.

We agree with the reviewer. The blood cancer/leukemia section has been expanded by adding relevant reports on the effects of Aloe vera, Aloe vera gel, and major bioactive compounds on leukemia-related models. We also clarified the leukemia subtype/cell line information where reported in the original studies, so that the discussion now covers both solid tumors and hematological malignancies more clearly.

3

Additionally, no studies addressing the combination of Aloe vera with chemotherapy/radiotherapy have been included. If such information is available, it should also be incorporated.

Thank you for pointing this out. We have added a focused discussion on the available evidence regarding Aloe vera or its bioactive compounds in combination with chemotherapy and/or radiotherapy. Where evidence is limited, this limitation has been stated clearly. The revised text also highlights the need for well-designed studies to evaluate potential synergistic effects, dose optimization, toxicity, and safety during combination treatment.

4

The authors should add a dedicated section outlining the gaps identified in the current literature and highlighting the additional studies required to validate both the anticancer effects and potential adverse effects of Aloe vera and its bioactive compounds.

We have added a dedicated section on current literature gaps and future research needs. This section discusses the limited number of clinical studies, lack of standardized Aloe vera preparations, variation in experimental models, insufficient toxicity data, limited pharmacokinetic evidence, and the need for validation of anticancer and adverse-effect profiles in preclinical and clinical settings.

5

The conclusion is overly long and could be shortened. Some content (e.g., lines 591–603) may be better placed in the section suggested in comment #4.

We agree with the reviewer. The conclusion has been shortened and made more focused. Content that was more suitable for discussing evidence gaps and future directions, including the material previously located around lines 591-603, has been moved to the new section on literature gaps and future research priorities.

6

Minor comments

Page # 7, lines 209-210 missing citation

The missing citation at Page 7, lines 209-210 has been added. The relevant statement is now supported by an appropriate reference.

7

Page # 7, lines 221-223, specify the type of leukemia cell line used for this study.

The leukemia cell line used in the referenced study has now been specified in the revised manuscript. This change improves the accuracy and reproducibility of the leukemia-related discussion.

8

Pages 15 &16, lines 43-438 missing citation

The missing citation(s) in the indicated section on Pages 15 and 16 have been added. We also rechecked the surrounding text to ensure that all mechanistic and experimental claims are properly supported by references.

Comment No.

Reviewer Comment

Authors' Response

General

The authors used a narrative review to “focus on the in vivo and in vitro anticancer potential of Aloe vera against various cancers, such as breast, cervical, hepatocellular, prostate, lung, blood, and colorectal cancers” (L91). However, this article has not fully answered some of the questions due to insufficient description.

We thank the reviewer for the detailed assessment of the manuscript. We agree that several areas required clearer explanation and stronger supporting evidence. The revised manuscript includes a more detailed methodology, clearer explanation of tabulated results, additional citations, and language improvements throughout the text.

1

First, the authors suggest “Keywords, such as Aloe vera, bioavailability, phytochemicals, oxidative stress, inflammation, anticancer activity or potential or mechanisms, breast cancer, lung cancer, clinical trials, and toxicity, besides Boolean operators (AND & OR) were used to scrutinize relevant studies.” (L99), which provides example search terms, but the exact search terms are not given, which hinders reproducibility. Without reproducibility, it is difficult for readers to believe what the authors did. The authors should add the descriptions regarding the exact search terms in method section.

Thank you for this important comment. We have revised the Methods section to provide the exact search terms and Boolean combinations used to identify the literature. The revised section now includes the databases searched, major keyword combinations, Boolean operators, screening approach, and eligibility criteria, thereby improving transparency and reproducibility.

2

Second, the authors suggest “Aloe vera reveals the protective effect against other types of cancer as well, which are demonstrated in Table 4.” (L555), but they did not explain the results of Table 4. The authors should explain these results in result section.

We agree with the reviewer. We have added an explanatory paragraph in the relevant results/discussion section to interpret Table 4. The revised text now summarizes the cancer models, Aloe vera preparations or bioactive compounds tested, major anticancer effects, and the mechanistic relevance of the findings presented in the table.

3

Finally, the authors described some of sentences without citation or justification as follows; “Nature has rewarded mankind with plants, facilitating the source of food, shelter, and medicine to improve the lifestyle and quality of life. These plants, especially medicinal plants, have been used since the ancient civilization to reduce disease severity and progression.” (L50), “Aloe vera, traditionally known as “plant of immortality”, is a miraculous plant of genus Aloe, promptly grown in the warm, dry, tropical, and subtropical climates.” (L65), “Aloe vera has gained valuable scientific attention for its potential role in oncology.” (L73), “Moreover, the abnormal cells develop multiple characteristics, including anti-growth signals’ insensitivity, and apoptosis evasion, consequently metastasize to the distant organs. The management of cancer is a global concern, although various medications and therapies, such as chemotherapy, radiotherapy, targeted therapy, immunotherapy, hormone therapy, radiation therapy, surgery, bone marrow transplant, and gene therapy, are available, but their adverse effects, like hair loss, fatigue, nausea, vomiting, immune-related inflammation, need to be managed by other supportive therapies. The emergence of plant-based therapeutic approaches has considerable importance due to their safe and effective outcomes.” (L78), “These characteristics and its widespread global distribution exaggerate its commercial and therapeutic significance.” (L117), “Phytochemicals are the plant-derived bioactive compounds, particularly responsible for the therapeutic and industrial reliability of plants. Various phytochemicals, such as polyphenols, flavonoids, phenolic acids, terpenoids, saponins, alkaloids, carotenoids, and glucosinolates, have been identified, contributing to promote individual health by attenuating disease severity and progression.” (L124), “Collectively, phytochemical diversity supports Aloe vera as a powerful natural resource for nutraceutical, cosmetic, pharmaceutical, and food industries.” (L138), “Bioavailability is the rate at which the drugs, compounds, and nutrients are getting absorbed and reaching the systemic circulation to provide specific health outcomes.Therefore, the absorption of bioactive compounds, derived from medicinal plants and providing multiple therapeutic attributes, is a global concern.” (L145), “Another study showed that a significant amount of compounds get transformed during absorption, i.e., an estimated absorption ranged from 5.51-6.60%, 6.60-11.32%, and 7.61-13.64% of aloin, aloe-emodin, and aloesin, respectively.” (L159), “Additionally, it has been reported that the oral Aloin intake has significant suboptimal absorption, however, as far as its bioavailability is concerned, it is only about 6%.” (L163), “The oral administration of aloin showed peak plasma levels of it after an hour of ingestion, however, it is excreted out from the body quickly, observed about 0.03% in the 24-hour urine, illustrating a significant portion of aloin either get metabolized or excreted in stools without being absorbed. Another study showed that the Aloe vera gel make the intestinal epithelial cells or gut wall more permeable by softening the barrier.” (L166), “Moreover, the bioavailability of fermented Aloe vera juice compounds, especially aloin, was significantly increased, significantly contributing to attenuate free radicals, oxidative stress, and its associated health impacts.” (L173), “Oxidative stress, caused by the imbalance of antioxidants and free radicals within the body, is a major health impact, contributing to the progression of various maladies, including cancer, cardiovascular disorders (CVD), liver diseases, and neurodegenerative disorders.” (L177), “The anticancer potential of Aloe vera has evidenced by various studies against different cancers, such as hepatocellular carcinoma (HCC), colon cancer, melanoma, lung cancer, breast cancer, and cervical  cancer.” (L206), “Furthermore, 2D and 3D cultures are used to explore the cancer suppressing effect of Aloe vera, which showed a remarkable decline in cell survival rate of HCC cell line with the provision of Aloe vera.” (L215), “In recent years there has been growing attention towards the role of polysaccharides found in Aloe vera in inhibiting colorectal cancer progression as well.” (L229), “Hepatocellular carcinoma is categorized into primary (mixed liver cancer and cholangiocarcinoma) and secondary (primary lymphoma, angiomyolipoma, and hepatoblastoma) cancer, which is progressed by the development of inflammation followed by hepatocyte damage, regeneration, and accumulation of genetic modifications. Aloe emodin, an anthraquinone typically extracted from Aloe vera exerts potent anti-inflammatory and anti-cancer effects. A study showed that Aloe emodin (AE) plays a significant role in regulating PI3K-AKT pathway, which is a key signaling pathway responsible for promoting cancer cell proliferation, survival, and resistance to apoptosis when abnormally activated in HCC, thereby inhibiting cancer cell proliferation and triggering apoptosis.” (L238), “Caspase-8 is mainly involved in the extrinsic apoptotic pathway that is activated through death receptors such as Fas.” (L260), “Human papillomavirus (HPV) is the most common cause of cervical cancers (~99%), with certain other factors, such as sedentary lifestyle and poor food practices.” (L283), “Aloe vera, a therapeutic medicinal plant, showed promising anticancer effects in various studies, significantly by targeting both viral infections, oncogenes, and tumor metastasis in cervical cancer cell lines.” (L296), “A distinct type of regulated cell death (RCD), also known as pyroptosis, has gained recent attention due to its unique pathway of cell death.” (L305), “It has been reported that Hela cells treated with Aloe emodin undergone cell death via the modulation of both apoptotic and pyroptotic pathways.” (L310), “The gel structure of Aloe vera also showed some promising anti-cancer potential. Aloe gel when combined with Alginate showed promising cytotoxicity by reducing cervical cancer cell viability. Additionally, the formation of Aloe-alginate hydrogel also improved the stability, adhesion, and delivery system, thereby allowing the compounds to be released slowly to prolong its therapeutic effect.” (L321), “Moreover, the activation of PI3K signalling pathway leads to the reduced apoptosis, uncontrolled metabolism, and excessive cell growth. Figure 6 describes the pathogenesis of CRC comprehensively.” (L350), “The management of CRC through medicinal plants, particularly Aloe vera, has attained significant attention due to their therapeutic attributes.” (L361), “Additionally, it also triggered apoptosis by activating pro-apoptotic protein (Bax), decreasing anti-apoptotic proteins, and blocking Akt and MEK pathways. Another anti-proliferative mechanism was observed when Aloe vera extract was combined with royal jelly and applied to non-small cell lung cancer cells.” (L406), “Alongside genetic modifications, several other factors, such as compromised immunity, radiation exposure, and carcinogenic chemicals, such as benzene, are involved in leukemia development.” (L436), “The gel structure of Aloe vera demonstrated geno-protective effect and showed hematological protection by restoring Hb, RBC, WBC, and reducing the number of blast cells. Moreover, an increase in arylesterase enzyme activity, which is responsible for breaking down harmful oxidants and restoration of thiol proteins, was also observed, highlighting Aloe vera’s role as a potent antioxidant.” (L444), “However, Aloe vera gel extract showed stronger cytotoxicity by inducing apoptosis through caspase independent pathway suggesting Aloe vera’s role as a promising natural anti-cancer agent.” (L456), “Its complex development and diverse symptoms require the need for effective treatment and prevention. The emergence of plant based therapeutic strategies in the recent years has gained considerable attention for its safe and more effective results with minimal sides effects.” (L462), “Results showed significant cytotoxic activity against MCF-7 cells with an IC50 value of 23 µg/mL in contrast to the IC50 value of 332 µg/mL in NIH-3T3 (normal cells), demonstrating low toxicity towards normal cells.” (467L), “However, certain major risk factors include impaired androgen metabolism, dietary modifications, ethnicity, mutated oncogenes, and age, as it mainly affects older men in the latter half of their lives.” (L491), “Androgen receptor is a protein that regulates prostate growth and is responsible for the development and progression of prostate cancer. Abnormal modulation of this protein can lead to increased prostate cells proliferation, thereby increasing the risk of mutation and cancer formation.” (L496), “Conventional treatments, such as surgery, chemotherapy, and radiation therapy, have significant adverse effects that can reduce the quality of life and are often limited to advanced metastatic cases as well. Moreover, resistance to chemotherapy is another major problem.” (L500), “A recent cell culture-based study has demonstrated that Aloe vera extract showed potent cytotoxic activity against DU145 prostate cancer cells.” (L507), “Beyond its influence on AR-dependent and AR-independent prostate cancer cells, the cytotoxic efficacy of aloe emodin also depends on P53 gene, that acts as a guardian and protects the cell from becoming cancerous. Another study investigated aloe emodin’s effect on prostate cancer cell lines, having different p53 status with LNCaP, DU-145, and PC3 having normal, mutated, and no p53 at all, respectively. The results demonstrated that LNCaP cells were the most sensitive while PC-3 cells were the least affected, concluding that aloe emodin works best when p53 is functional.” (L527), and “Another important investigation focused on Aloe vera gel extract on tumour suppressing and antioxidant properties against PC3 cells. The cytotoxicity was measured using MTT assay which demonstrated that Aloe vera gel extract reduced cancer cell viability in a dose dependent manner with stronger cytotoxic activity at 400 µg/ml was observed.” (L535), but it is difficult for readers to judge them without references as evidence for each description. Authors should add references for these descriptions.

We appreciate the reviewer for identifying these unsupported statements. We have reviewed all the indicated lines and added appropriate references wherever factual, mechanistic, epidemiological, or experimental claims were made. Statements that were too broad, unclear, or insufficiently supported have been revised or removed. We also ensured that claims regarding anticancer activity, bioavailability, apoptosis, oxidative stress, cancer risk factors, and cell-line findings are now directly linked to supporting citations.

4

Minor comment:

L22: “the associated adverse effects, which stimulated the development of plant-based bioactive compounds” may means that the associated adverse effects, which stimulated the development of plant-based bioactive compounds. The authors should revise the description.

The sentence at L22 has been revised to improve clarity and remove ambiguity. The revised wording now explains that the adverse effects of conventional anticancer therapies have encouraged interest in plant-derived bioactive compounds as supportive or complementary research candidates, without implying that adverse effects themselves directly 'stimulated' compound development.

5

Comments on the Quality of English Language

L22: “the associated adverse effects, which stimulated the development of plant-based bioactive compounds” may means that the associated adverse effects, which stimulated the development of plant-based bioactive compounds. The authors should revise the description.

Thank you for the language-related comment. The sentence at L22 and related wording in the abstract/introduction have been revised for grammatical clarity and scientific accuracy. The manuscript has also been reviewed for unclear wording, sentence structure, and consistency of terminology.

Comment No.

Reviewer Comment

Authors' Response

General

This review presents a comprehensive overview of the phytochemical composition, bioavailability, and anticancer mechanisms of Aloe vera. The topic is relevant and of interest to researchers working in natural products, oncology, and functional foods. The inclusion of graphical summaries, mechanistic figures, and cancer-specific tables improves the readability of the manuscript.

We sincerely thank the reviewer for the encouraging comments and for recognizing the relevance, scope, and readability of the manuscript. We have revised the manuscript to improve scientific rigor, critical analysis, translational balance, and language quality.

1

Major Comments

Overstatement of therapeutic potential

Several sections imply clinical efficacy of Aloe vera against cancer, whereas the majority of cited evidence is derived from in vitro and animal studies. The authors should more clearly distinguish preclinical findings from clinically validated outcomes and avoid statements suggesting established anticancer efficacy in humans.

We agree with the reviewer. The manuscript has been revised to avoid overstating the therapeutic potential of Aloe vera. We now clearly distinguish preclinical in vitro and animal evidence from clinically validated outcomes. Statements suggesting established anticancer efficacy in humans have been reworded to reflect the current evidence level and translational uncertainty.

2

Methodology of the review

The literature search strategy requires further detail. The authors mention searching databases between 2019 and 2025, but inclusion/exclusion criteria, study selection procedures, and screening methodology are insufficiently described. Consider adding a PRISMA-style flow diagram or a more rigorous methodology section.

Thank you for this important suggestion. The methodology section has been expanded to include the search strategy, databases, search terms, inclusion and exclusion criteria, study selection procedure, and screening approach. A PRISMA-style description/flow structure has also been added to make the review process more transparent and rigorous.

3

Critical appraisal is limited

The manuscript summarizes findings effectively but provides little critical evaluation of study quality, experimental limitations, reproducibility, or potential biases. A dedicated section discussing limitations of current evidence would strengthen the review.

We agree. A dedicated section discussing the limitations of the current evidence has been added. This section critically evaluates limitations related to study quality, small experimental datasets, variability in Aloe vera preparations, lack of reproducibility across models, limited toxicity data, and possible publication or selection bias.

4

Bioavailability and pharmacokinetics

Since bioavailability is highlighted in the title, this section could be expanded. More discussion on absorption, metabolism, toxicity, pharmacokinetic limitations, formulation strategies, and translational challenges is warranted.

The bioavailability and pharmacokinetics section has been expanded as suggested. The revised section now discusses absorption, metabolism, low oral bioavailability of key compounds, toxicity considerations, pharmacokinetic limitations, formulation strategies, and translational challenges that may affect the clinical relevance of Aloe vera-derived anticancer compounds.

5

Clinical evidence

The review would benefit from a separate section summarizing available human studies, clinical trials, or the absence thereof. This would help readers assess the translational significance of the reported findings.

We have added a separate discussion on clinical evidence and translational relevance. This section summarizes the limited availability of human studies and clinical trials, explains the current gap between preclinical findings and clinical application, and emphasizes the need for controlled clinical research before anticancer claims can be made for human use.

6

Minor Comments

Numerous grammatical and stylistic issues require careful language editing by a native English speaker or professional editing service.

The manuscript has undergone careful language editing to improve grammar, sentence structure, clarity, and scientific readability. Awkward wording and overly long sentences have been revised throughout the manuscript.

7

There are several typographical inconsistencies (e.g., spacing, punctuation, formatting of scientific terms and signaling pathways).

We have corrected typographical inconsistencies, including spacing, punctuation, capitalization, and formatting of scientific terms, signaling pathways, and abbreviations.

8

Some references appear incomplete, duplicated, or inconsistently formatted and should be checked carefully.

The reference list has been checked carefully. Incomplete and duplicated references have been corrected or removed, and the formatting has been made consistent according to journal requirements.

9

Species names such as Aloe vera should be consistently italicized throughout the manuscript.

Species names, including Aloe vera, have been checked and italicized consistently throughout the revised manuscript, including the title, abstract, main text, tables, and figure legends where applicable.

10

Several figures are informative but should be checked for resolution, labeling consistency, and readability.

All figures have been reviewed for resolution, labeling consistency, readability, and alignment with the revised text. Labels and legends have been improved where required.

11

Abbreviations should be defined at first appearance and used consistently throughout the text.

Abbreviations have been checked throughout the manuscript. Each abbreviation is now defined at first appearance and used consistently afterward.

12

The conclusion section could be shortened and focused more explicitly on future research priorities and clinical translation.

The conclusion has been shortened and refocused on the main findings, future research priorities, clinical translation, and the need for stronger preclinical and clinical validation.

13

Recommendation

Minor Revision to Moderate Revision

The manuscript addresses an important topic and contains substantial information; however, improvements in scientific rigor, critical analysis, discussion of translational limitations, and English language quality are recommended before publication.

We thank the reviewer for the recommendation and constructive guidance. The manuscript has been revised to address the concerns related to scientific rigor, critical analysis, translational limitations, and language quality.

14

Comments on the Quality of English Language

The manuscript is generally understandable and conveys the scientific content adequately; however, the English language requires substantial editing to improve clarity, grammar, and readability. Numerous grammatical errors, awkward sentence constructions, inconsistent verb tenses, incorrect word choices, and typographical issues are present throughout the text. In several instances, long and complex sentences reduce clarity and make the scientific arguments difficult to follow.
The manuscript would benefit from careful proofreading by a native English speaker or a professional language-editing service. Particular attention should be given to sentence structure, punctuation, subject–verb agreement, article usage, and consistency in scientific terminology. Additionally, some sections contain repetitive phrasing and could be revised for conciseness and improved flow.
Overall, the scientific message is clear, but significant language polishing is recommended to meet the standards expected for publication in an international journal.

We appreciate the detailed language feedback. The manuscript has been carefully edited to improve clarity, grammar, punctuation, subject-verb agreement, article usage, verb tense consistency, word choice, terminology, conciseness, and flow. Repetitive phrasing has also been reduced.

Comment No.

Reviewer Comment

Authors' Response

General

In this review article, the authors reviewed and discussed the in vivo and in vitro anticancer potential of Aloe vera against various cancers, such as breast, cervical, hepatocellular, prostate, lung, blood, and colorectal cancers.

Comments:
The reviewer has some concerns as follows:

This is an interesting review article. The reviewer has some comments:

We thank the reviewer for the positive comment and constructive concerns. We have revised the manuscript to make the focus on the anticancer effects of Aloe vera clearer and to reduce background material that was not directly related to the central aim of the review.

1

(1) The basic composition, functions, and therapeutic potential of Aloe vera have recently been reviewed and discussed in numerous review articles, such as Matei et al. 2025 (https://doi.org/10.3390/polysaccharides6020036), Sharma and Kaur, 2026 (https://doi.org/10.2174/0122103155339416241018063421), and Abid et al., 2025 (doi: 10.3389/fnut.2025.1689700). The present review article focuses on the anti-cancer effects of Aloe vera. Therefore, the basic composition and functions of Aloe vera do not require extensive explanation. It is recommended that the descriptions on pages 49-188 (Introduction to Antioxidant potential) be shortened.

Thank you for this useful suggestion. The background discussion on the basic composition, functions, and general therapeutic potential of Aloe vera has been shortened substantially. The revised manuscript now avoids extensive repetition of material already covered in recent reviews and focuses more directly on anticancer mechanisms, bioavailability, toxicity, and translational relevance.

2

(2) Why is the “Antioxidant potential” described in a separate paragraph? Readers are interested in its connection to the anti-cancer effects of Aloe vera. It is recommended that this be clearly explained.

We agree with the reviewer. The antioxidant potential section has been revised to clarify its connection with anticancer mechanisms. The revised text now explains how oxidative stress, redox imbalance, inflammation, apoptosis regulation, and ROS-mediated signaling may connect Aloe vera antioxidant activity to cancer-related pathways.

3

(3) In Figures 3-7, the related references need to be cited in the figure legends.

Relevant references have been added to the legends of Figures 3-7. The figure legends now cite the studies and mechanisms used to develop each figure.

4

(4) Paragraph 9 for “Synergistic effect of Aloe vera with other plants and phytochemicals” and Table 5 seem unnecessary, as its content is unrelated to the main topic of this manuscript, the anti-cancer effects of Aloe vera; or it can emphasize the synergistic anti-cancer effects of aloe vera with other plants and phytochemicals.

We have revised the section on synergistic effects and Table 5. Irrelevant general content has been removed, and the remaining content now focuses specifically on synergistic anticancer effects involving Aloe vera, Aloe vera-derived compounds, or combinations with other phytochemicals/plants where anticancer evidence is available.

5

(5) Please consider whether Figures 4 and 6 are necessary. It merely describes cervical cancer and colorectal cancer, respectively, and has nothing to do with the anti-cancer effects of Aloe vera; or perhaps the effects of Aloe vera could be incorporated into the figures.

Thank you for this helpful comment. Figures 4 and 6 have been revised so that they no longer only describe cervical and colorectal cancer pathogenesis. The revised figures now incorporate the reported Aloe vera-related anticancer mechanisms and show how Aloe vera or its bioactive compounds interact with the relevant cancer pathways.

6

(6) The Figure 2 appears to be not cited in the text. It can be revised.

Figure 2 has now been cited appropriately in the main text. The surrounding text has also been revised to improve the connection between the figure and the manuscript discussion.

7

Overall, this manuscript needs a revision.

We thank the reviewer for the overall recommendation. The manuscript has been revised throughout in response to the reviewer comments, with particular attention to focus, figure relevance, citations, and the connection between antioxidant and anticancer mechanisms.