Effects of Palm Tocotrienol-Rich Fraction Alone or in Combination with Glucosamine Sulphate on Grip Strength, Cartilage Structure and Joint Remodelling Markers in a Rat Model of Osteoarthritis

Round 1

Reviewer 1 Report

This is an appropriately conducted pre-clinical study reporting the effect of palm TRF and glucosamine sulphate in osteoarthritis rat models in reducing the weight and improving the grip strength
I have a few minor suggestions below.
- This is a pre-clinical study hence the “featured application” statement should be drafted based on the evidence from this study alone.
- Reference 3 need to be updated with the Global Burden fo Disease paper reporting the prevalence of OA.
- Please confirm the below sentence and back with the appropriate ref. The prevalence of 16% in age 15 years seems out of place.
“The pooled prevalence of knee OA was estimated to be 16.0% in the population aged 15 years and 22.9% in the population aged ≥40 years.”

Author Response

Dear Reviewer,

Thank you for the constructive comments. We have carefully considered your comments and responded in the attached response sheet. 

We look forward to receiving your positive reply. Thank you.

Author Response File: Author Response.pdf

Reviewer 2 Report

The manuscript “Effects of Palm Tocotrienol-rich Fraction Alone or in Combination with Glucosamine Sulphate on Grip Strength, Cartilage Structure and Joint Remodelling Markers in a Rat Model of Osteoarthritis” by Hiba Murtadha Al-Saadi, Kok-Yong Chin, Fairus Ahmad, Elvy Suhana Mohd Ramli, Azlan Mohd Arlamsyah, Fadhlullah Zuhair Japar Sidik, Juliana Abdul Hamid, Ima Nirwana Soelaiman is an article that aimed to compare the effects of palm tocotrienol-rich fraction (TRF), glucosamine sulphate and both agents combined in rats with osteoarthritis induced by monosodium iodoacetate (MIA).

Below are my comments and remarks regarding the article:
1. I propose in Figure 1 to add abbreviations of the groups of test animals (O, N T etc.)
2. The limitations have been described by the authors.
3. Most of the conclusions are more hypothetical than actually shown.

Author Response

Dear Reviewer,

Thank you for the constructive comments. We have carefully considered your comments and responded in the attached response sheet. 

We look forward to receiving a positive reply from you. Thank you.

Author Response File: Author Response.pdf

Reviewer 3 Report

My major concern about this study is the lack of results supporting the efficacy of the use of palm TRF to treat MIA-induced osteoarthritis (OA) in rats. The authors showed an improvement in grip strength and COMP levels but no effects were reported on cartilage damage. It would be important to add other experiments to support the efficacy of palm TRF. For example, cartilage markers in the tissues could be assessed by immunohistochemistry or synovial/infrapatellar fat pad inflammation could be evaluated to see if there is a decrease.

The introduction should be improved. In particular, OA is a disease involving all joint tissues and not only cartilage degeneration, synovitis and subchondral bone remodeling. Meniscus and ligaments are involved (DOI: 10.1007/s11420-011-9248-6). Moreover, fibrosis and inflammation of the infrapatellar fat pad in OA patients have been showed (DOI:10.3390/ijms21176016).  

The authors reported that they used 30 rats, 5 for each groups in the methods. However, it is reported that 7 rats were allocated in each group in figure 1. In the abstract, the authors reported that they used 36 rats. This point needs to be clarified.

Line 151: “um” should be corrected.

Table 1 should be cited in the text.

Figure 2: The values in the shaded area that are supposed to indicate a significant difference of the group compared to other groups are not clear. The authors should report not only if there is a difference but also the p-value. Regarding week 4, the authors reported that O group is significant compared to the O group of the same week.

Figure 2: week 0, the p-value of T+G vs G should be reported using the same layout used for other p-values.

Figure 3: The authors reported the presence of  a significant difference of the group at that week compared to other weeks (0-4) in the shaded area indicate. However, no p-value was reported.

Figure 4: The graphs are not clear. In particular, it is not clear what is the meaning of the cross etc. I suggest to better report these data. The reader should immediately see if there is a decrease or not of the score in the groups.

Figure 4B: the authors should use “T+G” and not “T-G” or “T G”.

In the caption of figure 4, it is not clear why the significant difference was set at  p<0.005 after Bonferroni correction instead of 0.05. The authors should consider to set the p-value at 0.05 and see if there are differences.

Author Response

Dear Reviewer,

Thank you for the constructive comments. We have carefully considered your comments and responded in the attached response sheet.

We look forward to receiving your positive reply. Thank you.

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

I have no more comments

Reviewer 3 Report

No additional comments.