Wound Healing Potential of Diterpenoids from the Hexane Fraction of Kaempferia galanga Rhizomes
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Abstract
Kaempferia galanga, a member of the Zingiberaceae family, is widely cultivated throughout Southeast Asia and traditionally used for the treatment of inflammation, pain, and dyspepsia. This study aimed to isolate compounds responsible for anti-inflammation and wound treatment from K. galanga. Bioassay-guided isolation of ethanol extract was used in this study. The hexane fraction from ethanol extract of K. galanga demonstrated significant activity by inhibiting nitric oxide released from LPS-stimulated RAW264.7 cells. It was then isolated to obtain the active compounds. Ten diterpenes (KG1-10) isolated from this fraction were investigated to determine their wound healing properties including anti-inflammatory effect using RAW264.7 cells, amelioration of human dermal fibroblasts (HDF) proliferation and migration, effect on collagen production and oxidative stress in H2O2-induced HDF cells. It was found that 6(-acetoxysandaracopimaradiene-1(, 9(-diol (KG6) displayed the most capable anti-inflammatory effect, with an IC50 value of 18.7 µM. This compound also showed good cell proliferation and migration on day 3 at 116.5% and 88.5%, respectively. Furthermore, 6(,14(-dihydroxyisopimara-8(9),15-diene (KG8) meaningfully increased the viable cell (119.7%) and extended migration of HDF cells (88.4%) which was preferable effect than that of allantoin (102.4, 75.5%). 6(-Acetoxysandaracopimaradiene-9(-ol (KG2) significantly increased the collagen content (38.7 μg/ml) in HDF cells. In addition, 1(-hydroxy-14(-methoxyisopimara-8(9),15-diene (KG7) exhibited the highest cytoprotective activity by increasing the viability of H2O2-induced oxidative damage in HDF cells to 92.1%. The hexane fraction was analyzed using gas chromatography to identify the presence of active wound healing compounds, KG1-10. This fraction showed significant potential as a pharmaceutical ingredient in wound treatment products due to its strong wound healing properties.
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Wild T, Rahbarnia A, Kellner M, Sobotka L, Eberlein T. Basics in nutrition and wound healing. Nutr. 2010; 26(9): 862-866. https://doi.org/10.1016/j.nut.2010.05.008
Gonzalez AC, Costa TF, Andrade ZD, Medrado AR. Wound healing-A literature review. An Bras Dermatol. 2016; 91: 614-620. https://doi.org/10.1590/abd1806-4841.20164741
Velnar T, Bailey T, Smrkolj V. The wound healing process: an overview of the cellular and molecular mechanisms. Int J Med Res. 2009; 37(5): 1528-1542. https://doi.org/10.1177/147323000903700531
Tonnesen MG, Feng X, Clark RA. Angiogenesis in wound healing. J InvestigDermatolSymp Proc. 2000; 5(1): 40-46. https://doi.org/10.1046/j.1087-0024.2000.00014.x
Houghton PJ, Hylands PJ, Mensah AY, Hensel A, Deters AM. In vitro tests and ethnopharmacological investigations: wound healing as an example. J Ethnopharmacol. 2005; 100(1-2): 100-107. https://doi.org/10.1016/j.jep.2005.07.001
Kumar A. Phytochemistry, pharmacological activities and uses of traditional medicinal plant Kaempferia galanga L.–An overview. J Ethnopharmacol. 2020; 253: 112667. https://doi.org/10.1016/j.jep.2020.112667
Pham NK, Nguyen HT, Nguyen QB. A review on the ethnomedicinal uses, phytochemistry and pharmacology of plant species belonging to Kaempferia L. genus (Zingiberaceae). Pharm Sci Asia. 2021; 48: 1-24. DOI: 10.29090/psa.2021.01.19.070
Tungcharoen P, Wattanapiromsakul C, Tansakul P, Nakamura S, Matsuda H, Tewtrakul S. Anti‐inflammatory effect of Isopimarane diterpenoids from Kaempferia galanga . Phytother Res. 2020; 34(3): 612-623. https://doi.org/10.1002/ptr.6549
Swapana N, Tominaga T, Elshamy AI, Ibrahim MA, Hegazy ME, Singh CB, Suenaga M, Imagawa H, Noji M, Umeyama A. Kaemgalangol A: Unusual seco-isopimaranediterpenoid from aromatic ginger Kaempferia galanga . Fitoterapia. 2018; 129: 47-53. DOI: 10.1016/j.fitote.2018.06.010
Elshamy AI, Mohamed TA, Swapana N, Yoneyama T, Noji M, Efferth T, Hegazy ME, Umeyama A. Cytotoxic polyoxygenatedIsopimarane diterpenoids from the edible rhizomes of Kaempferia galanga (kencur). Ind Crops Prod. 2020; 158: 112965. https://doi.org/10.1016/j.indcrop.2020.112965
Wisetsai A, Schevenels FT, Kanokmedhakul S, Kanokmedhakul K, Boonmak J, Youngme S, Suebrasri T, Lekphrom R. Isopimarane-type diterpenoids from the rhizomes of Kaempferia galanga L. and their biological activities. Nat Pro Res. 2021. https://doi.org/10.1080/14786419.2021.1989681
Longsri B, Kanpipit N, Puthongking P, Mahakunakorn P, Tiyaworanant S, Sungthong B, Thapphasaraphong S. Determination of a chemical marker in Dipterocarpusalatus oleoresin samples and bioactivity screening via antioxidants, nitric oxide inhibition on murine RAW 264.7 cells, and collagen production on normal human dermal fibroblasts. Trop J. Pharm Res. 2021; 5(5), 850-856. doi. org/10.26538/tjnpr/v5i5.10.
Sudsai T, Wattanapiromsakul C, Nakpheng T, Tewtrakul S. Evaluation of the wound healing property of Boesenbergia longiflora rhizomes. J Ethnopharmacol. 2013; 150(1): 223-231. https://doi.org/10.1016/j.jep.2013.08.038
Thanasakdecha S, Tewtrakul S. Wound healing gel containing compound 2α-acetoxysandaracopimaradien-1α-ol from Kaempferiamarginata rhizomes. J Herb Med. 2021; 28:100437. http://dx.doi.org/10.1016/j.hermed.2021.100437
Sudsai T, Prabpai S, Kongsaeree P, Wattanapiromsakul C, Tewtrakul S. Anti-inflammatory activity of compounds from Boesenbergia longiflora rhizomes. J Ethnopharmacol. 2014;154(2):453-461.https://doi.org/10.1016/j.jep.2014.04.034
Addis R, Cruciani S, Santaniello S, Bellu E, Sarais G, Ventura C, Maioli M, Pintore G. Fibroblast proliferation and migration in wound healing by phytochemicals: Evidence for a novel synergic outcome. Int J Medical Sci. 2020;17(8): 1030-1042. https://dx.doi.org/10.7150/Fijms.43986
Schäfer M, Werner S. Transcriptional control of wound repair. Annu. Rev. Cell Dev. Biol. 2007; 23:69-92. https://doi.org/10.1146/annurev.cellbio.23.090506.123609
Hashemi SA, Madani SA, Abediankenari S. The review on properties of Aloe vera in healing of cutaneous wounds. Biomed Res Int. 2015; 2015: 714216. https://doi.org/10.1155/2015/714216
Jia Y, Zhao G, Jia J. Preliminary evaluation: the effects of Aloe ferox Miller and Aloe arborescens Miller on wound healing. J Ethnopharmacol. 2008;120(2): 181-189. https://doi.org/10.1016/j.jep.2008.08.008
Araújo LU, Grabe-Guimarães A, Mosqueira VC, Carneiro CM, Silva-Barcellos NM. Profile of wound healing process induced by allantoin. Acta Cir Bras. 2010; 25(5): 460-466. https://doi.org/10.1590/s0102-86502010000500014
Werner S, Grose R. Regulation of wound healing by growth factors and cytokines. Physiol Rev. 2003; 83(3): 835-870. https://doi.org/10.1152/physrev.2003.83.3.835
Feghali CA, Wright TM. Cytokines in acute and chronic inflammation. Front Biosci-Landmark. 1997; 2(4): 12-26. DOI: https://doi.org/10.2741/a171
Ghatak S, Maytin EV, Mack JA, Hascall VC, Atanelishvili I, Moreno Rodriguez R, Markwald RR, Misra S. Roles of proteoglycans and glycosaminoglycans in wound healing and fibrosis. Int J Cell Biol. 2015; 2015:834893.
Mathew-Steiner SS, Roy S, Sen CK. Collagen in wound healing. Bioengineering. 2021; 8(5): 63.
Kanta J. The role of hydrogen peroxide and other reactive oxygen species in wound healing. Acta med (Hradec Kral). 2011; 54(3): 97-101. https://doi.org/10.14712/18059694.2016.28
Solleiro-Villavicencio H, Rivas-Arancibia S. Effect of chronic oxidative stress on neuroinflammatory response mediated by CD4+ T cells in neurodegenerative diseases. Front Cell Neurosci. 2018; 12: 114. https://doi.org/10.3389/fncel.2018.00114
Chokchaisiri R, Chaichompoo W, Chunglok W, Cheenpracha S, Ganranoo L, Phutthawong N, Bureekaew S, Suksamrarn A. Isopimarane diterpenoids from the rhizomes of Kaempferiamarginata and their potential anti-inflammatory activities. J Nat Pro. 2019; 83(1): 14-19. https://doi.org/10.1021/acs.jnatprod.9b00307
Muthachan T, Tewtrakul S. Anti-inflammatory and wound healing effects of gel containing Kaempferi amarginata extract. J Ethnopharmacol. 2019; 240: 111964. https://doi.org/10.1016/j.jep.2019.111964