Effect of Tinospora cordifolia-Derived Phytocomponents on Cancer: A Systematic Review

Round 1

Reviewer 1 Report

This is a review paper about effect of Tinospora cordifolia derived phytocomponents on cancer.

This review has accumulated a large amount of literature, but it was not sufficient for publication before the revision.

My suggestion are as follows：

Cancer threatens human health worldwide. During the previous research, a variety of natural products have been found to have anti-cancer activity in vivo and in vitro without toxic side effects. Why is the plant Tinospora cordifolia selected as the subject of this review? This should be stated clearly. Tinospora cordifolia is a plant in genus Tinospora. There are more than thirty species in this genus. Is there any similarity and difference between Tinospora cordifolia with other species in the same genus? Other plants in the same genus should be searched and compared to highlight the anti-cancer effectiveness of plant Tinospora cordifoli. The format and font need to be modified. For example, the plant name should be in italic, and “in vivo, in vitro” should be in italic, the font of title “4.3 Phytochemistry” in line 120, page 3, is not correct, etc.

Author Response

This review has accumulated a large amount of literature, but it was not sufficient for publication before the revision.

1) Cancer threatens human health worldwide. During the previous research, a variety of natural products have been found to have anti-cancer activity in vivo and in vitro without toxic side effects. Why is the plant Tinospora cordifolia selected as the subject of this review? This should be stated clearly.

Reply: The following sentence was added to the introduction portion:

Although, several studies have explored the therapeutic benefits of natural plant-based products, there is a relative deficit in the number of systematic reviews available, especially with respect to plants present in remote areas such as the Tinospora genus. In the Tenospora genus, only Tinospora cordifolia (Tc), has shown to exhibit anti-carcinogenic properties. Thus, Tc was selected as the subject of the review.

 

 

2) Tinospora cordifolia is a plant in genus Tinospora. There are more than thirty species in this genus. Is there any similarity and difference between Tinospora cordifolia with other species in the same genus? Other plants in the same genus should be searched and compared to highlight the anti-cancer effectiveness of plant Tinospora cordifoli.

Reply: The following sentence was added to the introduction portion:

Tc has shown to exhibit several unique features, distinguishing them from other closely related species in the Tinospora genus, including Tinospora malabarica (Tm). Tc has an ash coloured cork, a higher lenticels, nodes and internode, and a lower mucilage content than Tm.

 

3) The format and font need to be modified. For example, the plant name should be in italic, and “in vivo, in vitro” should be in italic, the font of title “4.3 Phytochemistry” in line 120, page 3, is not correct, etc.

Reply:  Corrections implemented

 

 

 

Note: All revised portions in the manuscript are highlighted in red

Author Response File: Author Response.pdf

Reviewer 2 Report

The manuscript (MS) entitled Effect of Tinospora cordifolia derived phytocomponents on cancer: A systematic review ' by Babji Deepa, Harsha V Babji, Jagadish V Hosmani, Abdul Wahab H Alamir, Shazia Mushtaq, A Thirumal Raj and Shankargouda Patil. The MS presents a review of the effect of Tinospora cordifolia extracts on cancer.

The manuscript needs major revision to be considered for publication in the Applied Science. The authors analyze in depth 25 original research articles investigating the anticancer properties of the extracts from Tc plant. And in the central part of the review – Discussion, subsection 4.3 – Phytochemistry they have only 19 sentences describing the anticancer properties of extracts. That is less than one sentence per article. In the Aims of Applied Science is explicitly written ‘Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible’. I encourage the authors to put more effort, to expand the review. Now that You have solid backbone, please put some ‘meat’ on it. Tables are good, informative, with relevant information.

Please support Your saying about synthetic nature of most of the chemotherapeutic agents in cancer treatment (from Conclusion) by relevant references. For example, it has been reported that approximately 49 % of 877 small molecules that were introduced as new pharmaceuticals between 1981 and 2002 by New Chemicals Entities were either natural products or semi-synthetic analogs or synthetic products based on natural product models. [Pramod Singh et al.; The Natural Products Journal, 3 (2013) 296]

Typos

line 53, 123 phytocompounents

Author Response

The manuscript needs major revision to be considered for publication in the Applied Science.

1) The authors analyze in depth 25 original research articles investigating the anticancer properties of the extracts fro0m Tc plant. And in the central part of the review – Discussion, subsection 4.3 – Phytochemistry they have only 19 sentences describing the anticancer properties of extracts. That is less than one sentence per article. In the Aims of Applied Science is explicitly written ‘Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible’. I encourage the authors to put more effort, to expand the review. Now that You have solid backbone, please put some ‘meat’ on it. Tables are good, informative, with relevant information.

Reply: The anti-carcinogenic effect of Tc is elaborated in the discussion by addition of details of its dosage and mechanisms of action

 

2) Please support Your saying about synthetic nature of most of the chemotherapeutic agents in cancer treatment (from Conclusion) by relevant references. For example, it has been reported that approximately 49 % of 877 small molecules that were introduced as new pharmaceuticals between 1981 and 2002 by New Chemicals Entities were either natural products or semi-synthetic analogs or synthetic products based on natural product models.

Reply: The authors have removed the line about the synthetic nature of chemotherapeutic agents. The conclusion is revised to focus on Tc.

 

3) Typos:  line 53, 123 phytocompounents.

Reply: Corrections implemented

 

Note: All revised portions in the manuscript are highlighted in red

Author Response File: Author Response.pdf

Reviewer 3 Report

The present study, on Tinospora cordifolia derived phytocomponents on cancer is impartment area in development of anticancer drugs from natural products. Authors has mainly focused on systematic review with available literature library. Authors need to include fallowing topics; mechanism of action, discussion on dose level effect, different type cancer induction and treatment approaches, identified active compounds and their mechanism. All these factors are impartment to understand the knowledge gap for further studies along with statistical based systematic review.

Author Response

The present study, on Tinospora cordifolia derived phytocomponents on cancer is impartment area in development of anticancer drugs from natural products.

 

1) Authors has mainly focused on systematic review with available literature library. Authors need to include fallowing topics; mechanism of action, discussion on dose level effect, different type cancer induction and treatment approaches, identified active compounds and their mechanism. All these factors are impartment to understand the knowledge gap for further studies along with statistical based systematic review.

Reply: Details of Tc dosage and mechanisms of action are added to the discussion

 

 

Note: All revised portions in the manuscript are highlighted in red

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

The manuscript should be accepted.

 

Author Response

The manuscript should be accepted. Reply: The authors thank the reviewer for the comments

Reviewer 2 Report

title: phytocomponents? According to the US National cancer institute, an IC50 value (drug concentration required for 50% inhibition in-vitro) of less than 100µg/ml from a medicinal plant is sufficient to be considered as an anticancer-agents. Reference needed! line 171: line 'Hexane fractions have induced apoptosis via caspase 3 activated DNase [26]' appears twice revisited manuscript is on much higher level than the original one. But, the review article should not be just summarizing the published work in one sentence. You should comment those results, put it in broader context, highlight the progress and the problems.

Author Response

Reviewer 2: 1) title: phytocomponents? Reply: The spelling error is corrected 2) According to the US National cancer institute, an IC50 value (drug concentration required for 50% inhibition in-vitro) of less than 100µg/ml from a medicinal plant is sufficient to be considered as an anticancer-agents. Reference needed! Reply: Reference 29 is added as the reference for the sentence 3) line 171: line 'Hexane fractions have induced apoptosis via caspase 3 activated DNase [26]' appears twice Reply: The repeated sentence is removed 4) The revisited manuscript is on much higher level than the original one. But, the review article should not be just summarizing the published work in one sentence. You should comment those results, put it in a broader context, highlight the progress and the problems. Reply: Sentences commenting on the results of the included studies are added. Note: All the revised content are highlighted in red in the revised manuscript

Author Response File: Author Response.pdf

Reviewer 3 Report

The authors have satisfactorily responded to all my questions and made the necessary changes to the manuscript.

 

Author Response

Reviewer 3:

The authors have satisfactorily responded to all my questions and made the necessary changes to the manuscript.

Reply: The authors thank the reviewer for the comments

 

Author Response File: Author Response.pdf