Anti-inflammatory Activity of Polyphenols from Labisia pumila Leaves Extract

Authors

  • Sharifah Norzi Syed Hassan Department of Bioprocess and Polymer Engineering, Faculty of Chemical and Energy Engineering, Universiti Teknologi Malaysia, 81310 UTM Johor Bahru, Johor, Malaysia
  • Rosnani Hasham ᵃDepartment of Bioprocess and Polymer Engineering, Faculty of Chemical and Energy Engineering, Universiti Teknologi Malaysia, 81310 UTM Johor Bahru, Johor, Malaysia; ᵇCentre for Sustainable Nanomaterials (CSNano), Universiti Teknologi Malaysia, 81310 UTM Johor Bahru, Johor, Malaysia; ᶜInnovation Centre in Agritechnology for Advanced Bioprocessing (ICA), Universiti Teknologi Malaysia, 84600 Pagoh, Johor, Malaysia
  • Siti Hajar Hashim Department of Bioprocess and Polymer Engineering, Faculty of Chemical and Energy Engineering, Universiti Teknologi Malaysia, 81310 UTM Johor Bahru, Johor, Malaysia
  • Mohd Amir Asyraf Mohd Hamzah ᵃDepartment of Bioprocess and Polymer Engineering, Faculty of Chemical and Energy Engineering, Universiti Teknologi Malaysia, 81310 UTM Johor Bahru, Johor, Malaysia; ᵈAdvanced Membrane Technology Research Centre (AMTEC), Universiti Teknologi Malaysia, 81310 UTM Johor Bahru, Johor, Malaysia

DOI:

https://doi.org/10.11113/mjfas.v20n2.3369

Keywords:

Labisia pumila, Anti-inflammatory, Polyphenols, Natural pain reliever, Plant extract

Abstract

Non-Steroidal Anti-inflammatory Drugs (NSAIDs) represent a class of pharmaceutical agents that are frequently misused and misconstrued within the medical landscape. While demonstrably efficacious in providing transient pain relief, NSAIDs do not effectively address the fundamental etiology of pain and are associated with a spectrum of potential adverse effects. Labisia pumila var alata also known as "Kacip Fatimah" has been traditionally used which is attributed to its antioxidant properties. Nonetheless, little attempt has been made to examine its antioxidant and anti-inflammatory characteristics. This study determined the molecular interactions and inhibitory activity profiles of L. pumila methanolic extract (LPE) against the corresponding enzymes via in chemico and in silico approaches. In chemico analysis was done on antioxidant activity and anti-inflammatory properties of L. pumila. The findings indicated that LPE exhibit the potent anti-inflammatory activity. Through high-performance liquid chromatography, it was shown that LPE had the highest gallic acid concentration at 10.74 ± 2.23 mg/mL. LPE did not exhibit cytotoxicity up to 100 µg/mL and displayed optimal protective against UVB-irradiation at 50 µg/mL towards HSF1184 Fibroblast cell line. LPE exhibited potent anti-inflammatory activity as it inhibited elastase and COX-2. Molecular docking studies indicated that gallic acid has a good affinity for collagenase (˗5.68 kcal/mol), elastase (˗4.88 kcal/mol) and COX 2 (˗4.91 kcal/mol). These findings collectively suggested that L. pumila extract has significant potential for the formulation of the natural anti-inflammatory remedies which offer a safer alternative treatment for pain relief, especially for long-term use replacing the conventional NSAIDs medicines.

References

R. Doomra, A. Goyal. (2020). NSAIDs and self-medication: A serious concern. J. Fam. Med. Prim. Care, 9, 2183. https://doi.org/10.4103/jfmpc.jfmpc_201_20.

H. Arif, S. Aggarwal. (2023). Salicylic acid (Aspirin), StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK519032/ (accessed December 28, 2023).

D. L. Conn, S. S. Lim. (2003). New role for an old friend: Prednisone is a disease-modifying agent in early rheumatoid arthritis. Curr. Opin. Rheumatol, 15, 193-196. https://doi.org/10.1097/00002281-200305000-00004.

B. Cohen, C. V. Preuss. (2023). Celecoxib. Essence Analg., 238-242. https://doi.org/10.1017/CBO9780511841378.056.

S. Kamel Oroumieh, L. Vanhaecke, R. Valizadeh, L. Van Meulebroek, A.A. Naserian. (2021). Effect of nanocurcumin and fish oil as natural anti-inflammatory compounds vs. glucocorticoids in a lipopolysaccharide inflammation model on Holstein calves’ health status. Heliyon, 7, e05894. https://doi.org/10.1016/j.heliyon.2020.e05894.

C. Nguyen-Ngo, J. C. Willcox, M. Lappas. (2020). Anti-inflammatory effects of phenolic acids punicalagin and curcumin in human placenta and adipose tissue. Placenta, 100, 1-12. https://doi.org/10.1016/j.placenta.2020.08.002.

Y. Gandhi, R. Kumar, J. Grewal, H. Rawat, S.K. Mishra, V. Kumar, S.K. Shakya, V. Jain, G. Babu, P. Sharma, A. Singh, R. Singh, R. Acharya. (2022). Advances in anti-inflammatory medicinal plants and phytochemicals in the management of arthritis: A comprehensive review. Food Chem. Adv., 1, 100085. https://doi.org/10.1016/j.focha.2022.100085.

N. ‘Izzah Ibrahim, I. N. Mohamed, N. Mohamed, E. S. Mohd Ramli, A. N. Shuid. (2022). The effects of aqueous extract of Labisia Pumila (Blume) Fern.-Vill. Var. Alata on wound contraction, hydroxyproline content and histological assessments in superficial partial thickness of second-degree burn model. Front. Pharmacol., 13. https://doi.org/10.3389/fphar.2022.968664.

M. Muhamad, C. Y. Choo, T. Hasuda, Y. Hitotsuyanagi. (2019). Estrogenic phytochemical from Labisia pumila (Myrsinaceae) with selectivity towards estrogen receptor alpha and beta subtypes. Fitoterapia, 137, 104256. https://doi.org/10.1016/j.fitote.2019.104256.

Y. Swarna Nantha, S. Vijayasingham, N. L. Adam, P. Vengadasalam, M. Ismail, N. Ali, L. C. Chang, L. Y. L. Ling, T. T. Tee, Y. H. Cheah. (2023). Labisia pumila standardized extract (SKF7®) reduces percentage of waist circumference and waist-to-height ratio in individuals with obesity. Diabetes. Obes. Metab., 25, 3298-3306. https://doi.org/10.1111/DOM.15229.

H. kyung Choi, D. hyun Kim, J. W. Kim, S. Ngadiran, M. R. Sarmidi, C. S. Park. (2010). Labisia pumila extract protects skin cells from photoaging caused by UVB irradiation. J. Biosci. Bioeng., 109, 291-296. https://doi.org/10.1016/j.jbiosc.2009.08.478.

E. Karimi, H. Z. E. Jaafar, S. Ahmad. (2013). Antifungal, anti-inflammatory and cytotoxicity activities of three varieties of labisia pumila benth: From microwave obtained extracts. BMC Complement. Altern. Med., 13, 1-10. https://doi.org/10.1186/1472-6882-13-20.

A. Yeop, J. Sandanasamy, S.F. Pang, J. Gimbun. (2021). Stability and controlled release enhancement of Labisia pumila’s polyphenols. Food Biosci., 41, 101025. https://doi.org/10.1016/j.fbio.2021.101025.

J. Bai, Y. Zhang, C. Tang, Y. Hou, X. Ai, X. Chen, Y. Zhang, X. Wang, X. Meng. (2021). Gallic acid: Pharmacological activities and molecular mechanisms involved in inflammation-related diseases. Biomed. Pharmacother, 133, 110985. https://doi.org/10.1016/J.BIOPHA.2020.110985.

D. Kammerer, A. Claus, A. Schieber, R. Carle. (2005). A novel process for the recovery of polyphenols from grape (Vitis vinifera L.) pomace. J. Food Sci., 70, C157-C163. https://doi.org/10.1111/j.1365-2621.2005.tb07077.x.

J. Wittenauer, S. MäcKle, D. Sußmann, U. Schweiggert-Weisz, R. Carle. (2015). Inhibitory effects of polyphenols from grape pomace extract on collagenase and elastase activity. Fitoterapia, 101, 179-187. https://doi.org/10.1016/j.fitote.2015.01.005.

M. K. H. Idris, R. Hasham, H. F. Ismail. (2022). Bioassay-Guided extraction of andrographis paniculata for intervention of in-vitro prostate cancer progression in metabolic syndrome environment, DARU. J. Pharm. Sci., 30, 253-272. https://doi.org/10.1007/s40199-021-00414-8.

M. A. A. Mohd Hamzah, R. Hasham, N. A. N. Nik Malek, Z. Hashim, M. Yahayu, F. I. Abdul Razak, Z. A. Zakaria. (2022). Beyond conventional biomass valorisation: pyrolysis-derived products for biomedical applications. Biofuel Res. J., 9, 1648-1658. https://doi.org/10.18331/brj2022.9.3.2.

K. V. Satardekar, M. A. Deodhar. (2010). Anti-ageing ability of terminalia species with special reference to hyaluronidase, elastase inhibition and collagen synthesis in vitro. Int. J. Pharmacogn. Phytochem. Res., 2, 30-34.https://www.researchgate.net/publication/285058243_Antiageing_ability_of_Terminalia_species_with_special_reference_to_hyaluronidase_elastase_inhibition_and_collagen_synthesis_in_vitro (accessed January 2, 2024).

Z. Rabiu, M. A. A. M. Hamzah, R. Hasham, Z. A. Zakaria. (2021). Characterization and antiinflammatory properties of fractionated pyroligneous acid from palm kernel shell. Environ. Sci. Pollut. Res., 28, 40535-40543. https://doi.org/10.1007/s11356-020-09209-x.

H. Mechqoq, S. Hourfane, M. El Yaagoubi, A. El Hamdaoui, J. R. G. da Silva Almeida, J. M. Rocha, N. El Aouad. (2022). Molecular docking, tyrosinase, collagenase, and elastase inhibition activities of argan by-products. Cosmetics, 9, 24. https://doi.org/10.3390/cosmetics9010024.

R. Othman, R. Othman, A. Baharuddin, N. R. Ramakrishnan, N. A. Rahman, R. Yusof, S. A. Karsani. (2017). Molecular docking studies of selected medicinal drugs as dengue virus-2 protease inhibitors. Sains Malaysiana, 46, 1865-1875. https://doi.org/10.17576/jsm-2017-4610-25.

D. Ramírez, J. Caballero. (2018). Is it reliable to take the molecular docking top scoring position as the best solution without considering available structural data? Molecules, 23, 1038. https://doi.org/10.3390/molecules23051038.

M. A. A. Mohd Hamzah, R. Hasham, N. A. N. Nik Malek, R. S. Raja Sulong, M. Yahayu, F. I. Abdul Razak, Z. A. Zakaria. (2022). Structural-based analysis of antibacterial activities of acid condensate from palm kernel shell, Biomass Convers. Biorefiner, 13, 4241-4253. https://doi.org/10.1007/s13399-021-02219-w.

L. Bravo. (1998). Polyphenols: Chemistry, dietary sources, metabolism, and nutritional significance. Nutr. Rev., 56317-333. https://doi.org/10.1111/J.1753-4887.1998.TB01670.X.

E. Karimi, H. Z. E. Jaafar, A. Ghasemzadeh. (2016). Chemical composition, antioxidant and anticancer potential of Labisia pumila variety alata under CO2 enrichment. NJAS - Wageningen J. Life Sci., 78, 85-91. https://doi.org/10.1016/j.njas.2016.05.002.

D. Turck, T. Bohn, J. Castenmiller, S. De Henauw, K. I. Hirsch-Ernst, A. Maciuk, I. Mangelsdorf, H. J. McArdle, A. Naska, C. Pelaez, K. Pentieva, A. Siani, F. Thies, S. Tsabouri, M. Vinceti, F. Cubadda, T. Frenzel, M. Heinonen, M. P. Maradona, R. Marchelli, M. Neuhäuser-Berthold, M. Poulsen, J. R. Schlatter, O. Albert, L. Matijević, H. K. Knutsen. (2022). Safety of an aqueous ethanolic extract of Labisia pumila as a novel food pursuant to Regulation (EU) 2015/2283. EFSA J., 20, e07611. https://doi.org/10.2903/j.efsa.2022.7611.

M. A. Awang, M. A. Z. Benjamin, A. Anuar, M. F. Ismail, S. D. Ramaiya, S. N. A. Mohd Hashim. (2023). Dataset of gallic acid quantification and their antioxidant and anti-inflammatory activities of different solvent extractions from Kacip Fatimah (Labisia pumila Benth. & Hook. f.) leaves. Data Br., 51, 109644. https://doi.org/10.1016/j.dib.2023.109644.

M. A. Ahmed Saeed, A. H. Memon, M. S. Ridzuan Hamil, H. K. Beh, S. A. Mohammed Saghir, G. Kaur, A. Sadikun, Z. Ismail. (2018). Toxicity evaluation of standardized and nanoliposomal extracts of Labisia pumila whole plant (Blume, Myrsinaceae) in Sprague Dawley rats. Trop. J. Pharm. Res., 17, 1557-1564. https://doi.org/10.4314/tjpr.v17i8.13.

G. Hostnik, J. Tošović, S. Štumpf, A. Petek, U. Bren. (2022). The influence of pH on UV/Vis spectra of gallic and ellagic acid: A combined experimental and computational study. Spectrochim. Acta Part A Mol. Biomol. Spectrosc., 267, 120472. https://doi.org/10.1016/J.SAA.2021.120472.

J. A. Morales-Del-Rio, M. Gutiérrez-Lomelí, M. A. Robles-García, J. A. Aguilar, E. Lugo-Cervantes, P. J. Guerrero-Medina, S. Ruiz-Cruz, F. J. Cinco-Moroyoqui, F. J. Wong-Corral, C. L. Del-Toro-Sánchez. (2015). Anti-inflammatory activity and changes in antioxidant properties of leaf and stem extracts from vitex mollis kunth during in vitro digestion. Evidence-Based Complement. Altern. Med., 2015. https://doi.org/10.1155/2015/349235.

B. D. Vanjare, Y. Seok Eom, H. Raza, M. Hassan, K. Hwan Lee, S. Ja Kim. (2022). Elastase inhibitory activity of quinoline analogues: Synthesis, kinetic mechanism, cytotoxicity, chemoinformatics and molecular docking studies. Bioorganic Med. Chem., 63. https://doi.org/10.1016/j.bmc.2022.116745.

K. Jakimiuk, J. Gesek, A. G. Atanasov, M. Tomczyk. (2021). Flavonoids as inhibitors of human neutrophil elastase. J. Enzyme Inhib. Med. Chem., 36, 1016-1028. https://doi.org/10.1080/14756366.2021.1927006.

S. H. Kim, H. S. Seo, B. H. Jang, Y. C. Shin, S. G. Ko. (2014). The effect of Rhus verniciflua Stokes (RVS) for anti-aging and whitening of skin. Orient. Pharm. Exp. Med., 14, 213-222. https://doi.org/10.1007/s13596-014-0152-8.

N. Petrovic, M. Murray. (2010). Using N,N,N’,N’-tetramethyl-p-phenylenediamine (TMPD) to assay cyclooxygenase activity in vitro. Methods Mol. Biol., 594, 129-140. https://doi.org/10.1007/978-1-60761-411-1_9.

R. Bisht, S. Bhattacharya, Y. A. Jaliwala. (2014). COX and LOX inhibitory potential of Abroma augusta and Desmodium gangeticum., J. Phytopharm., 3, 168-175. https://doi.org/10.31254/phyto.2014.3303.

K. K. Dong, N. Damaghi, S. D. Picart, N. G. Markova, K. Obayashi, Y. Okano, H. Masaki, S. Grether-Beck, J. Krutmann, K. A. Smiles, D. B. Yarosh. (2008). UV-induced DNA damage initiates release of MMP-1 in human skin. Exp. Dermatol., 17, 1037-1044. https://doi.org/10.1111/j.1600-0625.2008.00747.x.

S. H. Han, E. Ballinger, S. Y. Choung, J. Y. Kwon. (2022). Anti-photoaging effect of hydrolysates from pacific whiting skin via mapk/ap-1, nf-κb, tgf-β/smad, and nrf-2/ho-1 signaling pathway in uvb-induced human dermal fibroblasts. Mar. Drugs, 20, 308. https://doi.org/10.3390/md20050308.

H. Rezaei, A. Asefnejad, M. Daliri Joupari, S. Joughehdoust. (2021). The physicochemical and mechanical investigation of siloxane modified Gelatin/Sodium alginate injectable hydrogels loaded by ascorbic acid and β-Glycerophosphate. Mater. Today Commun., 26, 101914. https://doi.org/10.1016/j.mtcomm.2020.101914.

Y. Desmiaty, E. Mulatsari, F. Chany Saputri, M. Hanafi, R. Prastiwi, B. Elya. (2020). Inhibition of pancreatic elastase in silico and in vitro by Rubus rosifolius leaves extract and its constituents. J. Pharm. Bioallied Sci., 12, 317. https://doi.org/10.4103/JPBS.JPBS_271_19.

K. Eun Lee, S. Bharadwaj, U. Yadava, S. Gu Kang. (2019). Evaluation of caffeine as inhibitor against collagenase, elastase and tyrosinase using in silico and in vitro approach. J. Enzyme Inhib. Med. Chem., 34, 927-936. https://doi.org/10.1080/14756366.2019.1596904.

J. R. Vane, R. M. Botting. (2003). The mechanism of action of aspirin. Thromb. Res. Elsevier Ltd. 255-258. https://doi.org/10.1016/S0049-3848(03)00379-7.

J. K. Dhanjal, A. K. Sreenidhi, K. Bafna, S. P. Katiyar, S. Goyal, A. Grover, D. Sundar. (2015). Computational structure-based de novo design of hypothetical inhibitors against the anti- inflammatory target COX-2. PLoS One, 10. https://doi.org/10.1371/journal.pone.0134691.

P. H. F. Araújo, R. S. Ramos, J. N. da Cruz, S. G. Silva, E. F. B. Ferreira, L. R. de Lima, W. J. C. Macêdo, J. M. Espejo-Román, J. M. Campos, C. B. R. Santos. (2020). Identification of potential COX-2 inhibitors for the treatment of inflammatory diseases using molecular modeling approaches. Molecules, 25. https://doi.org/10.3390/MOLECULES25184183.

N. Borkakoti, F. K. Winkler, D. H. Williams, A. D’arcy, M. J. Broadhurst, P. A. Brown, W. H. Johnson, E. J. Murray. (1994). Structure of the catalytic domain of human fibroblast collagenase complexed with an inhibitor. Nat. Struct. Biol., 1, 106-110. https://doi.org/10.1038/nsb0294-106.

H. S. Roy, G. Dubey, V. K. Sharma, P. V. Bharatam, D. Ghosh. (2020). Molecular docking and molecular dynamics to identify collagenase inhibitors as lead compounds to address osteoarthritis. Https://Doi.Org/10.1080/07391102.2020.1838326.. https://doi.org/10.1080/07391102.2020.1838326.

H. Laronha, I. Carpinteiro, J. Portugal, A. Azul, M. Polido, K.T. Petrova, M. Salema-Oom, I. Barahona, J. Caldeira. (2021). Polymerizable matrix metalloproteinases’ inhibitors with potential application for dental restorations. Biomedicines, 9. https://doi.org/10.3390/BIOMEDICINES9040366.

Downloads

Published

24-04-2024