Antiasthmatic effect of <i>Curcuma aeruginosa</i> extract on isolated organ of the trachea

Swandari Paramita; Emil Bachtiar Moerad; Sjarif Ismail; Eva Marliana

doi:10.12688/f1000research.16416.1

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Research Article

Antiasthmatic effect of Curcuma aeruginosa extract on isolated organ of the trachea

[version 1; peer review: 1 approved with reservations, 2 not approved]

Swandari Paramita ^1,2, Emil Bachtiar Moerad³, Sjarif Ismail^2,4, Eva Marliana⁵

PUBLISHED 15 Nov 2018

Author details Author details

¹ Laboratory of Community Medicine, Faculty of Medicine, Mulawarman University, Samarinda, East Kalimantan, 75119, Indonesia
² Center for Medicine and Public Health Research, Institute for Research and Community Services, Mulawarman University, Samarinda, East Kalimantan, 75119, Indonesia
³ Department of Internal Medicine, Faculty of Medicine, Mulawarman University, Samarinda, East Kalimantan, 75119, Indonesia
⁴ Laboratory of Pharmacology, Faculty of Medicine, Mulawarman University, Samarinda, East Kalimantan, 75119, Indonesia
⁵ Laboratory of Organic Chemistry, Department of Chemistry, Faculty of Mathematics and Natural Sciences, Mulawarman University, Samarinda, East Kalimantan, 75119, Indonesia

Swandari Paramita
Roles: Conceptualization, Project Administration, Supervision, Writing – Review & Editing

Emil Bachtiar Moerad
Roles: Formal Analysis, Funding Acquisition, Resources

Sjarif Ismail
Roles: Data Curation, Methodology, Software, Writing – Original Draft Preparation

Eva Marliana
Roles: Investigation, Validation, Visualization

OPEN PEER REVIEW

REVIEWER STATUS

This article is included in the ICTROPS 2018 collection.

Abstract

Background: Asthma is a major health problem worldwide. Antiasthma drugs have side effects and can be expensive. It is important to develop antiasthma drugs from medicinal plants that have fewer side effects and are cheaper. One of the medicinal plants used for antiasthma treatment comes from Curcuma aeruginosa (Zingiberaceae family). The aim of the research is to examine spasmolytic activity of ethanol extract of C. aeruginosa on isolated guinea pig tracheas to determine the antiasthma effects.
Methods: The spasmolytic activity of C. aeruginosa extracts was tested in separated organs of guinea pig trachea. Guinea pig was sacrificed and its trachea rings were suspended in L-shaped wire loops in organ baths containing the Krebs solution aerated with carbogen. Isometric contractions of tracheal rings were measured by the transducer coupled to the amplifier. The trachea rings were exposed to DMSO as negative control, aminophylline as positive control and C. aeruginosa extracts. The single concentration-relaxation curve was obtained in every preparation.
Results: The result showed that the decrease of the spasmolytic activity in the guinea pig tracheal tone due to C. aeruginosa extract was significantly better (p=0.022) when compared to the negative control. Meanwhile, the EC₅₀ value of aminophylline (0.019 ± 0.05) was not significantly different (p=0.454) with C. aeruginosa (0.024 ± 0.05).
Conclusion: It could be concluded that C. aeruginosa extracts have the potency to be further developed as a new natural source of the antiasthma agents.

Keywords

antiasthma, Curcuma aeruginosa, spasmolytic

Corresponding author: Swandari Paramita

Competing interests: No competing interests were disclosed.

Grant information: This study was supported with funding from the Directorate General for Research and Development, Ministry of Research and Technology Higher Education of the Republic of Indonesia, for financing this research, as part of the implementation of Basic Research of Flagship University Year of 2018 No. 0045/E3/LL/2018.
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright: © 2018 Paramita S 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. Data associated with the article are available under the terms of the Creative Commons Zero "No rights reserved" data waiver (CC0 1.0 Public domain dedication).

How to cite: Paramita S, Moerad EB, Ismail S and Marliana E. Antiasthmatic effect of Curcuma aeruginosa extract on isolated organ of the trachea [version 1; peer review: 1 approved with reservations, 2 not approved]. F1000Research 2018, 7:1799 (https://doi.org/10.12688/f1000research.16416.1) First published: 15 Nov 2018, 7:1799 (https://doi.org/10.12688/f1000research.16416.1) Latest published: 15 Nov 2018, 7:1799 (https://doi.org/10.12688/f1000research.16416.1)

Introduction

Asthma is an inflammatory airway disease characterized by the occurrence of an respiratory airway hyper response and reversible narrowing of the airway¹. Asthma is one of the major non-communicable diseases in the world. About 235 million people worldwide suffer from asthma, particularly children. The strongest risk factors for developing asthma are a combination of genetic susceptibility to certain inhalable allergens and environmental exposure to them². Asthma medications are given to manage asthma sufferers³. Herbal preparations are one of the most popular complementary treatments used by asthmatic patients. Many important asthma drugs such as B2-agonists, anticholinergics, methylxanthines, and cromones have herbal origins⁴. Some medicinal plants have the effect of reducing smooth muscle stiffness, similar to the mechanism of asthma drugs, especially the anticholinergic drugs⁵. Research has also shown that some medicinal plants have the anti-inflammatory effects, following the same mechanism of corticosteroid drug used in asthma treatment⁶.

The genus Curcuma (family Zingiberaceae) consisting of more than 100 species is used widely as food a and in traditional medicines⁷. Indonesia is home to many species of Curcuma. The various species of Curcuma often used are C. longa (turmeric), C. xanthorrhiza, C. heyneana, C. aeruginosa, C. mangga, and C. zedoaria. Turmeric is the most frequently used plant for traditional medicine in Indonesia. C. aeruginosa considered as indigenous Curcuma species in Indonesia are currently not extensively studied, yet⁸.

Important medicinal plants from the genus Curcuma with anti-asthmatic potential include C. longa⁹. Other rhizomes of Curcuma species are traditionally used in the treatment of asthma, i.e. C. aeruginosa¹⁰, C. mangga¹¹, C. caesia¹², and C. zedoaria¹³. The antiasthma effects of C. aeruginosa are currently known, therefore, the objective of this study was to establish the tracheospasmolytic activity of C. aeruginosa applied on isolated tracheas of guinea pigs.

Method

Plant materials

The sampling of medicinal plants was conducted in Kutai Kartanegara District, East Kalimantan (0°59’51.1”S 116°58’33.1”E). Plants were then identified in the Faculty of Mathematics and Natural Sciences, Mulawarman University by comparing to the university herbarium collection.

Plant extractions

The rhizomes of C. aeruginosa were sliced and dried at room temperature for 3 days, crushed and transferred into a glass container. Approximately 1 kg of crushed rhizomes was soaked in 1 L of absolute ethanol (9401-03 Alcohol, Anhydrous, Reagent, J.T. Baker) for 5 days. The mixture was shaken occasionally with a shaker (3525 Incubator Orbital Shaker, Lab-Line, US). After 5 days, the materials were filtered (Whatman Filter Paper 11µm, Sigma-Aldrich) and evaporated using a rotary evaporator (RV06-ML Rotary Evaporator, IKA, Germany). The dried extracts were obtained and stored at 4°C in a dark bottle until use.

Experimental model

One male guinea pig (Cavia porcellus) (6 months old, 485 g) was obtained from Animal House Faculty of Medicine (Mulawarman University). They were treated in a controlled room temperature of 25°C, with a 12-hour light/dark cycle, and access to food pellets and filtered water ad libitum. The guinea pig was anesthetized intraperitoneally with a ketamine injection (Hameln Pharmaceuticals, Germany) at a dose of 60 mg/kg before the trachea was taken. After anesthetized, animals were euthanized by cervical dislocation. The trachea was quickly dissected by adhering fat and connective tissue of guinea pig.

Spasmolytic activity

The trachea rings were suspended in L-shaped wire loops in 10 ml organ baths (PL3508B6 Panlab Organ Bath System, ADInstruments), containing the Krebs solution (K3753 Krebs-Henseleit Buffer, Sigma-Aldrich) aerated with carbogen by maintaining the temperature at 37°C. Isometric contractions of tracheal rings were measured by the transducer (7004 Isometric Force Transducers, Ugo Basile) coupled to the amplifier (FE 221 BridgeAmp, ADInstruments) connected to PC running LabChart V5 software. An equilibration period of 90 minutes was done in Krebs solution. At the end of the equilibration period, the tracheal rings were stimulated with histamine in order to establish viability. After equilibration, the tracheal rings were exposed to DMSO (W387520 Methyl sulfoxide, Sigma-Aldrich) as the negative control, aminophylline (A1755 Aminophylline, Sigma-Aldrich) as positive control drugs and extract of C. aeruginosa according to the experimental protocol by Janbaz et al.¹⁴. The dosage for DMSO, aminophylline and plant extract were 0.0001, 0.0003, 0.001, 0.003, 0.01, and 0.03 mg/ml given 700, 750, 800, 850, 900, and 950 seconds after equilibration on the organ baths. The dose-response curve for trachea relaxation activity was obtained in every preparation.

Data analysis

Trachea relaxation activity is tabulated in the mean ± SD curve of the dose-response curve. The value of EC₅₀was calculated with Microsoft Excel 2016 as shown in Dataset 1. Data were analyzed using the Mann-Whitney because not normally distributed. All statistical analysis was performed using SPSS version 16.0 for Windows. A p-value of ≤ 0.05 was considered to be significant.

Ethical considerations

All protocols used in this experiment received approval from the Ethical Animal Care from the Medical and Health Research Ethics Commission, Faculty of Medicine, Mulawarman University No. 72/KEPK-FK/V/2018. All efforts were made to ameliorate any suffering of animals used in this research.

Results

The results of trachea relaxation between negative control, aminophylline, and C. aeruginosa extract presented in Figure 1. The result showed that the decrease of spasmolytic activity of C. aeruginosa extract was significantly better (p=0.000) than that in negative control. Meanwhile, the EC₅₀ value of aminophylline (0.019 ± 0.05) was not significantly different (p=0.454) with C. aeruginosa (0.024 ± 0.05), as shown in Figure 2.

Figure 1. Graph of trachea relaxation differences between C. aeruginosa (CA), aminophylline (A) as the positive control and negative control (N) in isolated trachea of guinea pig.

Figure 2. The EC₅₀ result on trachea relaxation between C. aeruginosa (CA) and aminophylline (A) as a positive control.

Dataset 1.Trachea relaxation between C. aeruginosa (CA), aminophylline (A) and negative control (N) and EC50 result on trachea relaxation between C. aeruginosa (CA) and aminophylline (A).

Discussion

C. aeruginosa (Supplementary File 1) is known in Indonesia as temu ireng or “pink and blue ginger” in English¹⁵. The color of fresh the rhizome can be yellows or greenish blue in color and mildly aromatic with a ginger-like aroma¹⁶. C. aeruginosa has been used as a traditional medicine in South and Southeast Asia¹⁷. The rhizomes have been used for gastrointestinal and uterine disorders, as well as parasitic and fungal infection¹⁸.

Other pharmacological activities of C. aeruginosa that have been reported include inhibition of HIV, anti-cancer activity, hepatoprotective, antiandrogenic, estrogenic properties, antimicrobial, antioxidant, antiplatelet-activating factor-like, antipyretic, antinociceptive, and anti-inflammatory¹⁹. Germacrone, zedoarone, dehydrocurdione, curcumenol, zedoarondiol, and isocurcumenol were chemical constituents from sesquiterpenes isolated from rhizomes of C. aeruginosa²⁰. In this study, the examination of antiasthma effects of C. aeruginosa has been reported. Further research is needed to identify the chemical compounds from C. aeruginosa that could convey antiasthma activity.

Conclusion

The results of this study indicate that ethanol extract of C. aeruginosa has an antiasthma effect based on the tracheospasmolytic activity. Therefore, C. aeruginosa can be developed as a possible source of new antiasthma drugs.

Data availability

F1000Research: Dataset 1. Trachea relaxation between C. aeruginosa (CA), aminophylline (A) and negative control (N) and EC50 result on trachea relaxation between C. aeruginosa (CA) and aminophylline (A)., 10.5256/f1000research.16416.d221690²¹

Grant information

This study was supported with funding from the Directorate General for Research and Development, Ministry of Research and Technology Higher Education of the Republic of Indonesia, for financing this research, as part of the implementation of Basic Research of Flagship University Year of 2018 No. 0045/E3/LL/2018.

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Supplementary material

Supplementary File 1: Picture of rhizome of Curcuma aeruginosa Roxb.

Click here to access the data

Faculty Opinions recommended

References

1. Barnes PJ: Asthma. In Harrison’s Principles of Internal Medicine. Nineteenth DL Kasper, SL Hauser, JL Jameson, AS Fauci, DL Longo and Loscalzo J, Eds. New York: McGraw-Hill Education, 2015; 1669–1681. Reference Source
2. World Health Organization: Factsheets: Asthma. World Health Organization. 2018. Reference Source
3. Chestnutt MS, Prendergast TJ: Pulmonary Disorders. In Current Medical Diagnosis & Treatment. Fifty-Sixt, MA Papadakis and SJ McPhee, Eds. New York: McGraw-Hill Education, 2017; 241–321. Reference Source
4. Karaman M, Firinci F, Cilaker S, et al.: Anti-inflammatory effects of curcumin in a murine model of chronic asthma. Allergol Immunopathol (Madr). 2012; 40(4): 210–214. PubMed Abstract | Publisher Full Text
5. Kumar A: Medicinal properties of Acorus calamus. J Drug Deliv Ther. 2013; 3(3): 143–144. Reference Source
6. Paramita S, Kosala K, Dzulkifli D, et al.: Anti-inflammatory activities of ethnomedicinal plants from dayak abai in North Kalimantan, Indonesia. Biodiversitas. 2017; 18(4): 1556–1561. Reference Source
7. Nararat A, Sirilun S, Julsrigival J, et al.: Chemical profiling and antimicrobial activity of essential oil from Curcuma aeruginosa Roxb., Curcuma glans K. Larsen & J. Mood and Curcuma cf. xanthorrhiza Roxb. collected in Thailand. Asian Pac J Trop Biomed. 2017; 7(10): 881–885. Publisher Full Text
8. Rahayu M, Sangat H, Lestari V: The Ethnobotanical Aspects of Curcuma spp. In Javanese Traditional Medicine. In Proceedings of 2nd International Symposium on Temulawak and 40th Meeting of National Working Group on Indonesian Medicinal Plant. 2011. Reference Source
9. Shakeri F, Soukhtanloo M, Boskabady MH: The effect of hydro-ethanolic extract of Curcuma longa rhizome and curcumin on total and differential WBC and serum oxidant, antioxidant biomarkers in rat model of asthma. Iran J Basic Med Sci. 2017; 20(2): 155–165. PubMed Abstract | Publisher Full Text | Free Full Text
10. Rajamma A, Bai V, Nambisan B: Antioxidant and antibacterial activities of oleoresins isolated from nine Curcuma species. Phytopharma. 2012; 2(2): 312–317. Reference Source
11. Dewangan MK, Dwivedi C, Sivna PL, et al.: Medicinal Value of Curcuma cassia Roxb: An Overview. Crit Rev Pharm Sci. 2014; 3(4): 1–9. Reference Source
12. Pakkirisamy M, Kalakandan S, Ravichandran K: Phytochemical Screening, GC-MS, FT-IR Analysis of Methanolic Extract of Curcuma caesia Roxb (Black Turmeric). Pharmacogn J. 2017; 9(6): 952–956. Publisher Full Text
13. Pathan A, Alshahrani A, Al-Marshad F: Pharmacological Effect of Curcuma zedoaria rhizomes on milk induced eosinophilia in the management of Asthma. Int J Ethnobiol Ethnomed. 2015; 1(1): 1–5. Reference Source
14. Janbaz KH, Hamid I, Mahmood MH, et al.: Bronchodilator, cardiotonic and spasmolytic activities of the stem barks of Terminalia arjuna. Can J Appl Sci. 2011; 1(3): 104–120. Reference Source
15. Nurcholis W, Priosoeryanto B, Purwakusumah E, et al.: Antioxidant, Cytotoxic Activities and Total Phenolic Content of Four Indonesian Medicinal Plants. Valensi. 2012; 2(4): 501–510. Reference Source
16. Srivilai J, Khorana N, Waranuch N, et al.: Anti-androgenic activity of furanodiene isolated from Curcuma aeruginosa Roxb. Extract. Naresuan Univ J. 2011; Special Is: 33–37. Reference Source
17. Hossain CF, Al-Amin M, Sayem AS, et al.: Antinociceptive principle from Curcuma aeruginosa. BMC Complement Altern Med. 2015; 15(1): 191. PubMed Abstract | Publisher Full Text | Free Full Text
18. Jose S, Thomas TD: Comparative phytochemical and anti-bacterial studies of two indigenous medicinal plants Curcuma caesia Roxb. and Curcuma aeruginosa Roxb. Int J Green Pharm. 2014; 8(1): 65–71. Reference Source
19. Theanphong O, Mingvanish W, Kirdmanee C: Chemical Constituents and Biological Activities of Essential Oil from Curcuma aeruginosa Roxb. Rhizome. Bull Heal Sci Technol. 2015; 13: 6–16. Reference Source
20. Suphrom N, Pumthong G, Khorana N, et al.: Anti-androgenic effect of sesquiterpenes isolated from the rhizomes of Curcuma aeruginosa Roxb. Fitoterapia. 2012; 83(5): 864–871. PubMed Abstract | Publisher Full Text
21. Paramita S, Moerad EB, Ismail S, et al.: Dataset 1 in: Antiasthmatic effect of Curcuma aeruginosa extract on isolated organ of the trachea. F1000Research. 2018. http://www.doi.org/10.5256/f1000research.16416.d221690

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Version 1

VERSION 1 PUBLISHED 15 Nov 2018

Author details Author details

¹ Laboratory of Community Medicine, Faculty of Medicine, Mulawarman University, Samarinda, East Kalimantan, 75119, Indonesia
² Center for Medicine and Public Health Research, Institute for Research and Community Services, Mulawarman University, Samarinda, East Kalimantan, 75119, Indonesia
³ Department of Internal Medicine, Faculty of Medicine, Mulawarman University, Samarinda, East Kalimantan, 75119, Indonesia
⁴ Laboratory of Pharmacology, Faculty of Medicine, Mulawarman University, Samarinda, East Kalimantan, 75119, Indonesia
⁵ Laboratory of Organic Chemistry, Department of Chemistry, Faculty of Mathematics and Natural Sciences, Mulawarman University, Samarinda, East Kalimantan, 75119, Indonesia

Swandari Paramita
Roles: Conceptualization, Project Administration, Supervision, Writing – Review & Editing

Emil Bachtiar Moerad
Roles: Formal Analysis, Funding Acquisition, Resources

Sjarif Ismail
Roles: Data Curation, Methodology, Software, Writing – Original Draft Preparation

Eva Marliana
Roles: Investigation, Validation, Visualization

Competing interests

No competing interests were disclosed.

Grant information

This study was supported with funding from the Directorate General for Research and Development, Ministry of Research and Technology Higher Education of the Republic of Indonesia, for financing this research, as part of the implementation of Basic Research of Flagship University Year of 2018 No. 0045/E3/LL/2018.
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Article Versions (1)

version 1

Published: 15 Nov 2018, 7:1799

https://doi.org/10.12688/f1000research.16416.1

Copyright

© 2018 Paramita S 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. Data associated with the article are available under the terms of the Creative Commons Zero "No rights reserved" data waiver (CC0 1.0 Public domain dedication).

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Paramita S, Moerad EB, Ismail S and Marliana E. Antiasthmatic effect of Curcuma aeruginosa extract on isolated organ of the trachea [version 1; peer review: 1 approved with reservations, 2 not approved]. F1000Research 2018, 7:1799 (https://doi.org/10.12688/f1000research.16416.1)

NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article.

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Current Reviewer Status: ?

Key to Reviewer Statuses VIEW HIDE

ApprovedThe 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 approvedFundamental flaws in the paper seriously undermine the findings and conclusions

Version 1

VERSION 1

PUBLISHED 15 Nov 2018

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Reviewer Report 08 Nov 2019

Sven-Erik Dahlén, Institute of Environmental Medicine (IMM), Karolinska Institute (KI), Stockholm, Sweden

Not Approved

https://doi.org/10.5256/f1000research.17935.r53982

The authors attempt to evaluate if an ethanolic extract of the plant Curcuma Aeruginosa possesses bronchodilatory actions in the guinea pig trachea. Figure 1 shows that the influence of the extract is no different from a presumed negative control (DMSO). ... Continue reading

The authors attempt to evaluate if an ethanolic extract of the plant Curcuma Aeruginosa possesses bronchodilatory actions in the guinea pig trachea. Figure 1 shows that the influence of the extract is no different from a presumed negative control (DMSO). The data therefore do not support the author’s conclusion that the extract has anti-asthmatic effects. The title of the manuscript is therefore wrong.

Specific major concerns:

Although figure 1 displays data without indications of the variability, the curves for the extract and the negative control are almost superimposed, whereas the curve for aminophylline shows the expected relaxation.
The calculations for Figure 2 are impossible to understand, and as far as I can see incorrect. EC 50 values are often calculated as 50% of the maximal response to e.g. a supramaximal dose of aminophylline. Here, it seems that the value causing 50% of the response to the highest dose tested (3 mg/mL) has been used for aminophylline, but this dose causes only 35% relaxation of the preparation. It is even more difficult to understand how an EC 50 value can be calculated for the extract because figure 1 indicates it causes no relaxation. In addition, the weight of an extract containing many undefined ingredients cannot be compared for potency with a pure pharmacologic agonist. The only comparison that would be relevant would be the qualitative documentation that the extract has bioactivity. The study has failed to show that.
The method description is unclear. Was the extract and the controls tested in a histamine-precontracted preparation, or only in a preparation kept at baseline tension?

Minor comments:

Why was DMSO the negative control? Was really the lyophilized extract dissolved in DMSO for the tests?
The dosage of DMSO is given in mg/mL and seems to be quite high.
The statement in the introduction suggesting that herbal preparations are popular for treatment of asthma is new to me. This needs to be referenced.
The description of the experimental protocol is incomplete, eg. dose of histamine not stated, the isometric load not defined, etc.
In the discussion, the authors report a number of pharmacologic activities of the extract. This would seem to preclude the use of the extract as many of the effects eg on endocrine regulation would be expected to be associated with adverse reactions.
The language of the manuscript needs language review. The wording is often imprecise and incorrect.

Is the work clearly and accurately presented and does it cite the current literature?

No
Is the study design appropriate and is the work technically sound?

No
Are sufficient details of methods and analysis provided to allow replication by others?

Partly
If applicable, is the statistical analysis and its interpretation appropriate?

No
Are all the source data underlying the results available to ensure full reproducibility?

No
Are the conclusions drawn adequately supported by the results?

No

Competing Interests: No competing interests were disclosed.

Reviewer Expertise: Airway pharmacology; Translational asthma research

I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above.

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Reviewer Report 03 Oct 2019

Waras Nurcholis, Department of Biochemistry, Faculty of Mathematics and Natural Sciences, IPB University, Bogor, Indonesia

Approved with Reservations

https://doi.org/10.5256/f1000research.17935.r53981

This manuscript mainly describes the antiasthmatic activity from ethanol extract of Curcuma aeruginosa rhizome. The work purpose is quite interesting but the organization is weak. So, the major decision was required for the following reasons.

In

This manuscript mainly describes the antiasthmatic activity from ethanol extract of Curcuma aeruginosa rhizome. The work purpose is quite interesting but the organization is weak. So, the major decision was required for the following reasons.

In title, please give information about your extract (ethanolic extract) and part used in this study (rhizome). I recommend changing the title to “Antiasthmatic activity from ethanol extract of Curcuma aeruginosa Roxb. rhizome”.
Please check and re-write some sentences in Abstract.
Introduction
- Paragraph 2. “The genus Curcuma … and in traditional medicines”. Please write the sentence with an appropriate meaning.
- Please add a reference in “Turmeric is the most…in Indonesia”.
- Please review in your introduction for several pharmacological activities from C. aeruginosa rhizome such as cytotoxicity¹, antioxidant² etc.
- Please create important novelty in your work in this article.
Method
- In spasmolytic activity:
  1. Please give information, how to calculate for trachea relaxation? Please give a calculation formula in your method.
  2. Please give information for negative control? Are you sure DMSO? Please explain more. Your data and in method must be in line.
- In plant extraction: Please give information for extract yield? Please give information for certificate analysis in your ethanolic extract or standardize your extract?
Results
- In Figure 1 and Figure 2, please show the value of significantly? Also, note in your figure. Analysis data with the results must be appropriate.
Discussion is poor of information. Please discuss more about your data. Please study more about antiasthmatic activity from medicinal plant extract and metabolite?
Conclusion: Please give information value for potency your sample in antiasthma activity?

Is the work clearly and accurately presented and does it cite the current literature?

Partly
Is the study design appropriate and is the work technically sound?

Partly
Are sufficient details of methods and analysis provided to allow replication by others?

Partly
If applicable, is the statistical analysis and its interpretation appropriate?

Partly
Are all the source data underlying the results available to ensure full reproducibility?

Yes
Are the conclusions drawn adequately supported by the results?

Partly

References

1. Nurcholis W, Khumaida N, Syukur M, Bintang M: Variability of curcuminoid content and lack of correlation with cytotoxicity in ethanolic extracts from 20 accessions of Curcuma aeruginosa RoxB. Asian Pacific Journal of Tropical Disease. 2016; 6 (11): 887-891 Publisher Full Text
2. Nurcholis W, Khumaida N, Syukur M, Bintang M: Variability of Total Phenolic and Flavonoid Content and Antioxidant Activity Among 20 Curcuma aeruginosa Roxb. Accessions of Indonesia. Asian Journal of Biochemistry. 2016; 11 (3): 142-148 Publisher Full Text

Competing Interests: No competing interests were disclosed.

Reviewer Expertise: Biochemistry

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.

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Reviewer Report 12 Sep 2019

Ian Sinha, Institute of Translational Medicine, University of Liverpool, Liverpool, UK

Not Approved

https://doi.org/10.5256/f1000research.17935.r53554

This is an interesting paper. Cumin has been shown to have potential anti-inflammatory effects in other papers, and I think you should do a proper literature review around this - you will need to incorporate this in both your background ... Continue reading

This is an interesting paper. Cumin has been shown to have potential anti-inflammatory effects in other papers, and I think you should do a proper literature review around this - you will need to incorporate this in both your background and discussion which are both focussed on cumin but not asthma.

I am not sure why you chose aminophylline rather than a better bronchodilator such as salbutamol, and you will need to explain the limitation of looking at the trachea in an animal model, rather than being able to evaluate the small airways.

Nonetheless, this is an interesting paper.

Is the work clearly and accurately presented and does it cite the current literature?

Partly
Is the study design appropriate and is the work technically sound?

Partly
Are sufficient details of methods and analysis provided to allow replication by others?

Yes
If applicable, is the statistical analysis and its interpretation appropriate?

Yes
Are all the source data underlying the results available to ensure full reproducibility?

Yes
Are the conclusions drawn adequately supported by the results?

Yes

Competing Interests: No competing interests were disclosed.

Reviewer Expertise: Paediatric asthma.

I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above.

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Ian Sinha, University of Liverpool, Liverpool, UK
Waras Nurcholis, IPB University, Bogor, Indonesia
Sven-Erik Dahlén, Karolinska Institute (KI), Stockholm, Sweden

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08 Nov 2019 | for Version 1

Sven-Erik Dahlén, Institute of Environmental Medicine (IMM), Karolinska Institute (KI), Stockholm, Sweden

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Not Approved

The authors attempt to evaluate if an ethanolic extract of the plant Curcuma Aeruginosa possesses bronchodilatory actions in the guinea pig trachea. Figure 1 shows that the influence of the extract is no different from a presumed negative control (DMSO). The data therefore do not support the author’s conclusion that the extract has anti-asthmatic effects. The title of the manuscript is therefore wrong.

Specific major concerns:

Although figure 1 displays data without indications of the variability, the curves for the extract and the negative control are almost superimposed, whereas the curve for aminophylline shows the expected relaxation.
The calculations for Figure 2 are impossible to understand, and as far as I can see incorrect. EC 50 values are often calculated as 50% of the maximal response to e.g. a supramaximal dose of aminophylline. Here, it seems that the value causing 50% of the response to the highest dose tested (3 mg/mL) has been used for aminophylline, but this dose causes only 35% relaxation of the preparation. It is even more difficult to understand how an EC 50 value can be calculated for the extract because figure 1 indicates it causes no relaxation. In addition, the weight of an extract containing many undefined ingredients cannot be compared for potency with a pure pharmacologic agonist. The only comparison that would be relevant would be the qualitative documentation that the extract has bioactivity. The study has failed to show that.
The method description is unclear. Was the extract and the controls tested in a histamine-precontracted preparation, or only in a preparation kept at baseline tension?

Minor comments:

Why was DMSO the negative control? Was really the lyophilized extract dissolved in DMSO for the tests?
The dosage of DMSO is given in mg/mL and seems to be quite high.
The statement in the introduction suggesting that herbal preparations are popular for treatment of asthma is new to me. This needs to be referenced.
The description of the experimental protocol is incomplete, eg. dose of histamine not stated, the isometric load not defined, etc.
In the discussion, the authors report a number of pharmacologic activities of the extract. This would seem to preclude the use of the extract as many of the effects eg on endocrine regulation would be expected to be associated with adverse reactions.
The language of the manuscript needs language review. The wording is often imprecise and incorrect.

Is the work clearly and accurately presented and does it cite the current literature?

No
Is the study design appropriate and is the work technically sound?

No
Are sufficient details of methods and analysis provided to allow replication by others?

Partly
If applicable, is the statistical analysis and its interpretation appropriate?

No
Are all the source data underlying the results available to ensure full reproducibility?

No
Are the conclusions drawn adequately supported by the results?

No

Competing Interests

No competing interests were disclosed.

Reviewer Expertise

Airway pharmacology; Translational asthma research

I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above.

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Reviewer Report

14 Views

03 Oct 2019 | for Version 1

Waras Nurcholis, Department of Biochemistry, Faculty of Mathematics and Natural Sciences, IPB University, Bogor, Indonesia

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Approved With Reservations

This manuscript mainly describes the antiasthmatic activity from ethanol extract of Curcuma aeruginosa rhizome. The work purpose is quite interesting but the organization is weak. So, the major decision was required for the following reasons.

In title, please give information about your extract (ethanolic extract) and part used in this study (rhizome). I recommend changing the title to “Antiasthmatic activity from ethanol extract of Curcuma aeruginosa Roxb. rhizome”.
Please check and re-write some sentences in Abstract.
Introduction
- Paragraph 2. “The genus Curcuma … and in traditional medicines”. Please write the sentence with an appropriate meaning.
- Please add a reference in “Turmeric is the most…in Indonesia”.
- Please review in your introduction for several pharmacological activities from C. aeruginosa rhizome such as cytotoxicity¹, antioxidant² etc.
- Please create important novelty in your work in this article.
Method
- In spasmolytic activity:
  1. Please give information, how to calculate for trachea relaxation? Please give a calculation formula in your method.
  2. Please give information for negative control? Are you sure DMSO? Please explain more. Your data and in method must be in line.
- In plant extraction: Please give information for extract yield? Please give information for certificate analysis in your ethanolic extract or standardize your extract?
Results
- In Figure 1 and Figure 2, please show the value of significantly? Also, note in your figure. Analysis data with the results must be appropriate.
Discussion is poor of information. Please discuss more about your data. Please study more about antiasthmatic activity from medicinal plant extract and metabolite?
Conclusion: Please give information value for potency your sample in antiasthma activity?

Is the work clearly and accurately presented and does it cite the current literature?

Partly
Is the study design appropriate and is the work technically sound?

Partly
Are sufficient details of methods and analysis provided to allow replication by others?

Partly
If applicable, is the statistical analysis and its interpretation appropriate?

Partly
Are all the source data underlying the results available to ensure full reproducibility?

Yes
Are the conclusions drawn adequately supported by the results?

Partly

References

1. Nurcholis W, Khumaida N, Syukur M, Bintang M: Variability of curcuminoid content and lack of correlation with cytotoxicity in ethanolic extracts from 20 accessions of Curcuma aeruginosa RoxB. Asian Pacific Journal of Tropical Disease. 2016; 6 (11): 887-891 Publisher Full Text
2. Nurcholis W, Khumaida N, Syukur M, Bintang M: Variability of Total Phenolic and Flavonoid Content and Antioxidant Activity Among 20 Curcuma aeruginosa Roxb. Accessions of Indonesia. Asian Journal of Biochemistry. 2016; 11 (3): 142-148 Publisher Full Text

Competing Interests

No competing interests were disclosed.

Reviewer Expertise

Biochemistry

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.

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Reviewer Report

10 Views

12 Sep 2019 | for Version 1

Ian Sinha, Institute of Translational Medicine, University of Liverpool, Liverpool, UK

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Not Approved

This is an interesting paper. Cumin has been shown to have potential anti-inflammatory effects in other papers, and I think you should do a proper literature review around this - you will need to incorporate this in both your background and discussion which are both focussed on cumin but not asthma.

I am not sure why you chose aminophylline rather than a better bronchodilator such as salbutamol, and you will need to explain the limitation of looking at the trachea in an animal model, rather than being able to evaluate the small airways.

Nonetheless, this is an interesting paper.

Is the work clearly and accurately presented and does it cite the current literature?

Partly
Is the study design appropriate and is the work technically sound?

Partly
Are sufficient details of methods and analysis provided to allow replication by others?

Yes
If applicable, is the statistical analysis and its interpretation appropriate?

Yes
Are all the source data underlying the results available to ensure full reproducibility?

Yes
Are the conclusions drawn adequately supported by the results?

Yes

Competing Interests

No competing interests were disclosed.

Reviewer Expertise

Paediatric asthma.

I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above.

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[1] 1. Barnes PJ: Asthma. In Harrison’s Principles of Internal Medicine. Nineteenth DL Kasper, SL Hauser, JL Jameson, AS Fauci, DL Longo and Loscalzo J, Eds. New York: McGraw-Hill Education, 2015; 1669–1681. Reference Source

[2] 2. World Health Organization: Factsheets: Asthma. World Health Organization. 2018. Reference Source

[3] 3. Chestnutt MS, Prendergast TJ: Pulmonary Disorders. In Current Medical Diagnosis & Treatment. Fifty-Sixt, MA Papadakis and SJ McPhee, Eds. New York: McGraw-Hill Education, 2017; 241–321. Reference Source

[4] 4. Karaman M, Firinci F, Cilaker S, et al.: Anti-inflammatory effects of curcumin in a murine model of chronic asthma. Allergol Immunopathol (Madr). 2012; 40(4): 210–214. PubMed Abstract | Publisher Full Text

[5] 5. Kumar A: Medicinal properties of Acorus calamus. J Drug Deliv Ther. 2013; 3(3): 143–144. Reference Source

[6] 6. Paramita S, Kosala K, Dzulkifli D, et al.: Anti-inflammatory activities of ethnomedicinal plants from dayak abai in North Kalimantan, Indonesia. Biodiversitas. 2017; 18(4): 1556–1561. Reference Source

[7] 7. Nararat A, Sirilun S, Julsrigival J, et al.: Chemical profiling and antimicrobial activity of essential oil from Curcuma aeruginosa Roxb., Curcuma glans K. Larsen & J. Mood and Curcuma cf. xanthorrhiza Roxb. collected in Thailand. Asian Pac J Trop Biomed. 2017; 7(10): 881–885. Publisher Full Text

[8] 8. Rahayu M, Sangat H, Lestari V: The Ethnobotanical Aspects of Curcuma spp. In Javanese Traditional Medicine. In Proceedings of 2nd International Symposium on Temulawak and 40th Meeting of National Working Group on Indonesian Medicinal Plant. 2011. Reference Source

[9] 9. Shakeri F, Soukhtanloo M, Boskabady MH: The effect of hydro-ethanolic extract of Curcuma longa rhizome and curcumin on total and differential WBC and serum oxidant, antioxidant biomarkers in rat model of asthma. Iran J Basic Med Sci. 2017; 20(2): 155–165. PubMed Abstract | Publisher Full Text | Free Full Text

[10] 10. Rajamma A, Bai V, Nambisan B: Antioxidant and antibacterial activities of oleoresins isolated from nine Curcuma species. Phytopharma. 2012; 2(2): 312–317. Reference Source

[11] 11. Dewangan MK, Dwivedi C, Sivna PL, et al.: Medicinal Value of Curcuma cassia Roxb: An Overview. Crit Rev Pharm Sci. 2014; 3(4): 1–9. Reference Source

[12] 12. Pakkirisamy M, Kalakandan S, Ravichandran K: Phytochemical Screening, GC-MS, FT-IR Analysis of Methanolic Extract of Curcuma caesia Roxb (Black Turmeric). Pharmacogn J. 2017; 9(6): 952–956. Publisher Full Text

[13] 13. Pathan A, Alshahrani A, Al-Marshad F: Pharmacological Effect of Curcuma zedoaria rhizomes on milk induced eosinophilia in the management of Asthma. Int J Ethnobiol Ethnomed. 2015; 1(1): 1–5. Reference Source

[14] 14. Janbaz KH, Hamid I, Mahmood MH, et al.: Bronchodilator, cardiotonic and spasmolytic activities of the stem barks of Terminalia arjuna. Can J Appl Sci. 2011; 1(3): 104–120. Reference Source

[15] 15. Nurcholis W, Priosoeryanto B, Purwakusumah E, et al.: Antioxidant, Cytotoxic Activities and Total Phenolic Content of Four Indonesian Medicinal Plants. Valensi. 2012; 2(4): 501–510. Reference Source

[16] 16. Srivilai J, Khorana N, Waranuch N, et al.: Anti-androgenic activity of furanodiene isolated from Curcuma aeruginosa Roxb. Extract. Naresuan Univ J. 2011; Special Is: 33–37. Reference Source

[17] 17. Hossain CF, Al-Amin M, Sayem AS, et al.: Antinociceptive principle from Curcuma aeruginosa. BMC Complement Altern Med. 2015; 15(1): 191. PubMed Abstract | Publisher Full Text | Free Full Text

[18] 18. Jose S, Thomas TD: Comparative phytochemical and anti-bacterial studies of two indigenous medicinal plants Curcuma caesia Roxb. and Curcuma aeruginosa Roxb. Int J Green Pharm. 2014; 8(1): 65–71. Reference Source

[19] 19. Theanphong O, Mingvanish W, Kirdmanee C: Chemical Constituents and Biological Activities of Essential Oil from Curcuma aeruginosa Roxb. Rhizome. Bull Heal Sci Technol. 2015; 13: 6–16. Reference Source

[20] 20. Suphrom N, Pumthong G, Khorana N, et al.: Anti-androgenic effect of sesquiterpenes isolated from the rhizomes of Curcuma aeruginosa Roxb. Fitoterapia. 2012; 83(5): 864–871. PubMed Abstract | Publisher Full Text

[21] 21. Paramita S, Moerad EB, Ismail S, et al.: Dataset 1 in: Antiasthmatic effect of Curcuma aeruginosa extract on isolated organ of the trachea. F1000Research. 2018. http://www.doi.org/10.5256/f1000research.16416.d221690

Antiasthmatic effect of Curcuma aeruginosa extract on isolated organ of the trachea

Abstract

Keywords

Introduction

Method

Plant materials

Plant extractions

Experimental model

Spasmolytic activity

Data analysis

Ethical considerations

Results

Figure 1. Graph of trachea relaxation differences between C. aeruginosa (CA), aminophylline (A) as the positive control and negative control (N) in isolated trachea of guinea pig.

Figure 2. The EC50 result on trachea relaxation between C. aeruginosa (CA) and aminophylline (A) as a positive control.

Discussion

Conclusion

Data availability

Grant information

Supplementary material

References

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Figure 2. The EC₅₀ result on trachea relaxation between C. aeruginosa (CA) and aminophylline (A) as a positive control.