Proven Inhibitory Effect on Lipopolysaccharides- Induced Nitric Oxide Production of Zanthoxylum rhetsa under Accelerated Condition and Stability Affecting Factors

Authors

  • Chureeporn Imphat Graduate school on Applied Thai Traditional Medicine program, Faculty of Medicine, Thammasat University, Pathum Thani 12120, Thailand
  • Pakakrong Thongdeeying Department of Applied Thai Traditional Medicine, Faculty of Medicine, Thammasat University, Pathum Thani 12120, Thailand.Center of Excellence in Applied Thai Traditional Medicine Research (CEATMR), Thammasat University, Pathum Thani 12120, Thailand.
  • Arunporn Itharat Department of Applied Thai Traditional Medicine, Faculty of Medicine, Thammasat University, Pathum Thani 12120, Thailand. Center of Excellence in Applied Thai Traditional Medicine Research (CEATMR), Thammasat University, Pathum Thani 12120, Thailand.
  • Sumalee Panthong Department of Applied Thai Traditional Medicine, Faculty of Medicine, Thammasat University, Pathum Thani 12120, Thailand. Center of Excellence in Applied Thai Traditional Medicine Research (CEATMR), Thammasat University, Pathum Thani 12120, Thailand.
  • Sunita Makchuchit Center of Excellence in Applied Thai Traditional Medicine Research (CEATMR), Thammasat University, Pathum Thani 12120, Thailand.

Keywords:

Zanthoxylum rhetsa, Nitric oxide, Osteoarthritis, Stability, Forced degradation

Abstract

Introduction: Zanthoxylum rhetsa preparations were used in ethnomedicine for the treatments of muscle and tendon spasms. The essential oil from its fruit has been reported for its anti-inflammatory activity and previous study has shown that the hexane extract of Z.rhetsa pericarp showed highest in vitro anti-inflammatory effect. Nitric oxide (NO) is an inflammatory mediator associated with osteoarthritis. Therefore, in vitro production inhibition of NO in RAW264.7 macrophages was performed. The accelerated stability test and the forced degradation test were studied to estimate storage life and to ensure appropriate conditions for its activity.

Methods: The hexane extracts obtained from the pericarp (PHE), fruit (FHE) and seed (SHE) were tested for production inhibition of LPS-induced NO in RAW264.7 macrophages. The active extract was treated with accelerated storage conditions and stress conditions and assessed for the LPS-induced NO production inhibition.

Results: PHE showed the most potent activities on NO (IC50 11.99 ± 1.66 μg/ml) production inhibition but less active than prednisolone. After accelerated stability test, the activity of PHE was less stable than 30 days. Forced degradation on PHE revealed that oxidation condition did not affect NO production inhibition while moisture, heat and alkaline conditions weakened its activity. The acidic condition rendered PHE to be inactive.

Conclusion: PHE was the most active fraction for NO production inhibition associated with osteoarthritis. Its estimated shelf-life was between 9 to 12 months at room temperature. However, moisture, heat, alkaline, and acid conditions should be avoided in order to maintain its activity.

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References

Litwic A, Edwards M, Dennison E, Cooper C. Epidemiology and burden of osteoarthritis. Br Med Bull. 2013;105:185-199.

National Statistic office. The 2014 survey of the older persons in Thailand. Bangkok, Thailand: Text and Journal Publication; 2014.

National Statistic office. Report on the 2017 survey of the older persons in Thailand. Bangkok, Thailand: Text and Journal Publication; 2018.

Wittenauer R, Smith L, Aden K. Update on 2004 Background Paper, BP 6.12 Osteoarthritis. https://www.who.int/medicines/areas/priority_medicines/BP6_12Osteo.pdf. Published 2013. Accessed February 4, 2021.

Kumar S, Singh RK, Bhardwaj TR. Therapeutic role of nitric oxide as emerging molecule. Biomed Pharmacother. 2017;85:182-201.

Dhawan V. Reactive oxygen and nitrogen species: General considerations. In: Ganguly NK, Jindal SK, Biswal S, Barnes PJ, Pawankar R, eds. Studies on Respiratory Disorders. York, England: Springer science & business media; 2014:27-47.

Ashkavand Z, Malekinejad H, Vishwanath BS. The pathophysiology of osteoarthritis. J Pharm Res. 2013;7:132-138.

International Association for the Study of Pain. IASP announces revised definition of pain. https://www.iasp-pain.org/PublicationsNews/NewsDetail.aspx?ItemNumber=10475. Published 2020. Accessed February 4, 2021.

Smitinand T. Thai Plant Names (Revised edition). Bangkok, Thailand: National office of Buddhism press; 2014.

Department of Thai Traditional and Alternative Medicine. Pra-O-Sod-Pra-Na-Rai Scripture. Bangkok, Thailand: The War Veterans Organization of Thailand; 2012.

Medicine Regulation Division. Thai Traditional Household Remedy. https://www.fda.moph.go.th/sites/drug/SitePages/Law03-07.aspx. Published 2013. Accessed February 4, 2021.

Brantner AH, Zoeschg J, Pfeifhofer H, et al. Evaluation of Zanthoxylum limonella essential oil and ethanolic fruit extract for their biological activities. In: International Congress and 53rd Annual Meeting of the Society for Medicinal Plant Research; August 21-25, 2005; Florence, Italy. Abstract 153.

Netweera V, Priprem A, Limsittichaikoon S. In vitro and in vivo studies of a bioadhesive gel containing volatile oil extracted from fruits of Zanthoxylum limonella Alston. IJSRP. 2016;6(1):175-178.

Imphat C, Chairat N, Chinacarawat N, inventor; Mae Fah Luang University, assignee. Massage oil product containing Zanthoxylum limonella fruit essential oil. Thailand patent No. 11339. March 17, 2016.

Imphat C, Thongdeeying P, Itharat A, et al. Anti-inflammatory investigations of extracts of Zanthoxylum rhetsa. Evid Based Complementary Altern Med. 2021;2021(Article ID 5512961):1-15. doi: 10.1155/2021/5512961.

Huynh-Ba K. Introduction. In: Huynh-Ba K, ed. Handbook of stability testing in pharmaceutical development. New York, USA: Springer science & business media; 2009:1-6.

Blessy M, Patel RD, Prajapati PN, Agrawal YK. Development of forced degradation and stability indicating studies of drugs-a review. J Pharm Anal. 2014;4(3):159-165.

Makchuchit S, Rattarom R, Itharat A. The anti-allergic and anti-inflammatory effects of benjakul extract (a Thai traditional medicine), its constituent plants and its some pure constituents using in vitro experiments. Biomed Pharmacother. 2017;89:1018-1026.

European Medicine Agency. ICH topic Q1A (R2) stability testing of new drug substances and products, Note for guidance on stability testing: stability testing of new drug substances and products (CPMP/ICH/2736/99). London, England: EMEA; 2006.

Makchuchit S, Ruangnoo S, Itharat A. Investigation of anti-Allergic and anti-inflammatory activities of prasaprohyai ethanolic extract under forced degradation and accelerated storage conditions. TMJ. 2019;19(2):371-384.

Lotz M, Hashimoto S, Kühn K. Mechanism of chondrocyte apoptosis. Osteoarthr Cartil. 1999;7:389-391.

Tripathi P, Thipathi Pr, Kashyap L, Singh V. The Role of nitric oxide in inflammatory reactions. FEMS Immunol Med Mic. 2007;51:443-452.

Hieu NV, Hoa NV, Hoai KT, et al. Inhibitory effect on nitric oxide production of essential oil from Zanthoxylum rhetsa (Roxb.) DC. fruit. J Pharmacogn Phytochem. 2020;9(5):67-70.

Turek C, Stintzing FC. Stability of essential oils: a review. Compr Rev Food Sci Saf. 2013;12:40-53.

Salah S, Awadallah H, Karaman R. Pain Killers. In: Karaman R, ed. Commonly Used Drugs. New York, USA: Nova Science Publishers; 2015:75-129.

Institute of Ayurveda (Chevaka Komarapat). Thai traditional pharmacy textbook. Bangkok, Thailand: Foundation of Thai Traditional Medicine, Applied; 2016.

Srirattananont N. Phytochemical study of Zanthoxylum limonella (Dennst.) Alston pericarp. Master’ s thesis. Mahidol University; 2010.

Wei D, Wang L, Liu C, Wang B. β-sitosterol solubility in selected organic solvents. J Chem Eng Data. 2010;55:2917-2919.

National Center for Biotechnology Information. PubChem compound summary for CID 259846, Lupeol. https://pubchem.ncbi.nlm.nih.gov/compound/Lupeol. Published 2021. Accessed May 28, 2021.

Geetha T, Varalakshmi P, Mary LR. Effect of triterpenes from Crataeva nurvala stem bark on lipid peroxidation in adjuvant induced arthritis in rats. Pharmacol Res. 1998;37(3):191-195.

Fernández MA, Heras B, Garcia MD, Sáenz MT, Villar A. New insight into the mechanism of action of the anti-inflammatory triterpene lupeol. J Pharm Pharmacol. 2001;53(11):1533-1539.

Srisamatthakarn P, Wattanawikkit P, Ammawath S. Effect of explant and extraction conditions on the physical-chemical and antioxidant properties of Mah-khwuaen (Zanthoxylum limonella Alston) Extract. Songklanakarin J Pl Sci. 2017;4(3):75-81.

U.S. Department of Health and Human Services. Guidance for industry Q1E evaluation of stability data. Rockville, USA: Office of Training and Communication; 2004.

Kumar GR, Chandrashekar BS, Lukose O, Ravindra M, Ravikumar K. Evaluation of in-vitro antioxidant property and total phenolic content of Zanthoxylum rhetsa fruit extracts. J Pharmacogn Phytochem. 2019;8(3):1139-1144.

Tukun AB, Shaheen N, Banu CP, Mohiduzzaman Md, Islam S, Begum M. Antioxidant capacity and total phenolic contents in hydrophilic extracts of selected Bangladeshi medicinal plants. Asian Pac J Trop Med. 2014;7(Suppl 1):S568-S573.

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Published

2021-08-27

How to Cite

[1]
Imphat, C., Thongdeeying, P., Itharat, A., Panthong, S. and Makchuchit, S. 2021. Proven Inhibitory Effect on Lipopolysaccharides- Induced Nitric Oxide Production of Zanthoxylum rhetsa under Accelerated Condition and Stability Affecting Factors. Asian Medical Journal and Alternative Medicine. 21, 2 (Aug. 2021), 134–144.

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Original Articles