熊果酸

熊果酸（英語：Ursolic acid，也譯為烏索酸，3-β-羥基-熊果-12-烯-28-羧酸，3-beta-3-hydroxy-urs-12-ene-28-oic-acid）是一種五環三萜物質，最早在1920年發現於蘋果的表皮蠟質中。熊果酸也存在於許多植物的果皮中以及迷迭香、麝香草等草藥中。

Ursolic acid
IUPAC名 (1S,2R,4aS,6aR,6aS,6bR,8aR,10S,12aR,14bS)-10-Hydroxy-1,2,6a,6b,9,9,12a-heptamethyl-2,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydro-1H-picene-4a-carboxylic acid[1]
系統名 (1R,2S,5S,8R,9S,10S,14R,15R,18S,20R)-18-hydroxy-1,2,8,9,15,19,19-heptamethylpe ntacyclo[12.8.0.02,11.05,10.015,20]docos-11-ene-5-carboxylic acid (1R,2S,5S,8R,9S,10S,14R,15R,18S,20R)-1,2,8,9,15,19,19-七甲基-18-羥基五環[12.8.0.02,11.05,10.015,20]-11-二十二烯-5-甲酸
別名	Prunol, Malol, beta-Ursolic acid, NSC4060, CCRIS 7123, TOS-BB-0966, 3-beta-hydroxyurs-12-en-28-oic acid[1]
識別
CAS號	77-52-1  Y
PubChem	64945
ChemSpider	58472
SMILES	O=C(O)[C@@]54[C@H](/C3=C/C[C@H]1[C@](CC[C@@H]2[C@]1(C)CC[C@H](O)C2(C)C)(C)[C@]3(C)CC4)[C@@H](C)[C@H](C)CC5
InChI	1/C30H48O3/c1-18-10-15-30(25(32)33)17-16-28(6)20(24(30)19(18)2)8-9-22-27(5)13-12-23(31)26(3,4)21(27)11-14-29(22,28)7/h8,18-19,21-24,31H,9-17H2,1-7H3,(H,32,33)/t18-,19+,21+,22-,23+,24+,27+,28-,29-,30+/m1/s1
InChIKey	WCGUUGGRBIKTOS-GPOJBZKABB
ChEBI	9908
性質
化學式	C30H48O3
摩爾質量	456.7 g·mol−1
熔點	285 - 288 °C（270 K）
若非註明，所有數據均出自標準狀態（25 ℃，100 kPa）下。

自然發生

熊果酸存在於許多植物，如紫茉莉^[2]以及日常生活中使用的許多水果和草藥（例如蘋果、羅勒、越桔、蔓越莓、接骨木花、薄荷、迷迭香、薰衣草、牛至、百里香、山楂和李子）中。蘋果皮含有大量的熊果酸以及相關化合物。 ^[3]

潛在的生物化學作用

已經研究了熊果酸的許多潛在生化作用，但是沒有臨床研究表明它對人類健康有益。在體外，熊果酸通過抑制STAT3激活途徑抑制各種類型癌細胞的增殖，^{[4] [5]}並且還可以減少癌細胞的增殖並誘導細胞凋亡。 ^[6]熊果酸也已顯示能抑制JURK白血病T細胞的JNK表達和IL-2活化，導致增殖和T細胞活化的減少。^[7]熊果酸是一種弱芳香酶抑制劑（IC₅₀ = 32μM），^[8]並且已經顯示當添加到餵養給小鼠的飲食中時增加肌肉和棕色脂肪的量並減少白色脂肪肥胖和相關病症。 在生理濃度下，熊果酸還誘導了eryptosis（有缺陷的紅血球中的類似凋亡的細胞自殺死亡）。 ^[9]已經發現它可以減少肌肉萎縮並刺激小鼠的肌肉生長，也顯示出潛在的心臟保護作用。 ^[10]

在小鼠中，熊果酸在坐骨神經損傷後誘導神經再生。^[11] 熊果酸可改善多摩酸誘導的小鼠認知功能障礙。^[12] 熊果酸可通過阻斷內質網應激和IκB激酶β/核因子-κB介導的炎症通路來改善高脂飲食引起的認知障礙。 ^[13] 熊果酸通過抑制p38 /NF-κB介導的炎症途徑減輕脂多糖誘導的小鼠大腦認知功能障礙。^[14] 熊果酸可改善認知障礙並減輕D-半乳糖誘導的衰老小鼠大腦中的氧化損傷。^[15]熊果酸可促進部分肝切除術後小鼠肝臟的再生。 ^[16]在以高脂飲食餵養的鏈脲佐菌素誘導的糖尿病小鼠中，熊果酸可增強細胞免疫系統和胰腺β細胞功能。^[17]UA增加骨骼肌質量，以及握力和運動能力。 增強耐力，減少與肌肉萎縮發展有關的基因的表達，並減少累積疲勞和運動引起的壓力的指標。 ^[18]

在大鼠中，熊果酸改善了高脂飲食誘導的肝脂肪變性，並改善了高脂飲食誘導的非酒精性脂肪肝疾病的代謝紊亂。 ^[19]

用途

熊果酸可以在用於化妝品添加劑的植物中發現。 熊果酸可以作為合成更有效的生物活性衍生物的起始材料，例如實驗性抗腫瘤劑。 ^[20]

請參見

• 樺木酸
• 模繞酮酸
• 齊墩果酸

參考文獻

1. CID 64945 from PubChem
2. Constituents of Mirabilis jalapa. Siddiqui S., Siddiqui B.S., Adil Q. and Begum S., Fitoterapia, 1990, Volume 61, No. 5, page 471 (abstract （頁面存檔備份，存於網際網路檔案館）)
3. Ursolic acid from apple pomace and traditional plants: A valuable triterpenoid with functional properties. Food Chem. April 2017, 220: 477–489. PMID 27855928. doi:10.1016/j.foodchem.2016.10.029.
4. Ursolic acid inhibits nuclear factor-kappaB activation induced by carcinogenic agents through suppression of IkappaBalpha kinase and p65 phosphorylation: correlation with down-regulation of cyclooxygenase 2, matrix metalloproteinase 9, and cyclin D1 (PDF). Cancer Res. 2003, 63 (15): 4375–83 [2020-03-02]. PMID 12907607. （原始內容存檔 (PDF)於2013-02-21）.
5. Pathak AK; Bhutani M; Nair AS; et al. Ursolic acid inhibits STAT3 activation pathway leading to suppression of proliferation and chemosensitization of human multiple myeloma cells. Mol. Cancer Res. 2007, 5 (9): 943–55. PMID 17855663. doi:10.1158/1541-7786.MCR-06-0348.
6. Wang X, Zhang F, Yang L, Mei Y, Long H, Zhang X, Zhang J, Qimuge-Suyila, Su X.,"Ursolic acid inhibits proliferation and induces apoptosis of cancer cells in vitro and in vivo", J Biomed Biotechnol. 2011;2011:419343 Full-text pdf （頁面存檔備份，存於網際網路檔案館）
7. Kaewthawee, Narawan; Brimson, Sirikalaya. The Effects of Ursolic Acid on Cytokine Production via the MAPK Pathways in Leukemic T-Cells (PDF). EXCLI. February 2013, 12 (February): 102–114 [2020-03-02]. （原始內容存檔 (PDF)於2013-05-25）.
8. Gnoatto, SC; Dassonville-Klimpt, A; Da Nascimento, S; Galéra, P; Boumediene, K; Gosmann, G; Sonnet, P; Moslemi, S. Evaluation of ursolic acid isolated from Ilex paraguariensis and derivatives on aromatase inhibition. European Journal of Medicinal Chemistry. 2008, 43 (9): 1865–77. PMID 18192087. doi:10.1016/j.ejmech.2007.11.021.
9. Triggering of erythrocyte cell membrane scrambling by ursolic acid. J Nat Prod. 2011, 74 (10): 2181–2186. PMID 21923134. doi:10.1021/np2005133.
10. Uncoupling and antioxidant effects of ursolic acid in isolated rat heart mitochondria. J. Nat. Prod. July 2011, 74 (7): 1640–4. PMID 21648406. doi:10.1021/np200060p.
11. Liu, Biao; Liu, Yan; Yang, Guang; Xu, Zemin; Chen, Jiajun. Ursolic acid induces neural regeneration after sciatic nerve injury. Neural Regeneration Research. 2013-09-25, 8 (27): 2510–2519. ISSN 1673-5374. PMC 4145935 . PMID 25206561. doi:10.3969/j.issn.1673-5374.2013.27.002.
12. Wu, Dong-mei; Lu, Jun; Zhang, Yan-qiu; Zheng, Yuan-lin; Hu, Bin; Cheng, Wei; Zhang, Zi-feng; Li, Meng-qiu. Ursolic acid improves domoic acid-induced cognitive deficits in mice. Toxicology and Applied Pharmacology. 2013-09-01, 271 (2): 127–136. ISSN 1096-0333. PMID 23707761. doi:10.1016/j.taap.2013.04.038.
13. Lu, Jun; Wu, Dong-mei; Zheng, Yuan-lin; Hu, Bin; Cheng, Wei; Zhang, Zi-feng; Shan, Qun. Ursolic acid improves high fat diet-induced cognitive impairments by blocking endoplasmic reticulum stress and IκB kinase β/nuclear factor-κB-mediated inflammatory pathways in mice. Brain, Behavior, and Immunity. 2011-11-01, 25 (8): 1658–1667. ISSN 1090-2139. PMID 21708244. doi:10.1016/j.bbi.2011.06.009.
14. Wang, Yong-Jian; Lu, Jun; Wu, Dong-mei; Zheng, Zi-hui; Zheng, Yuan-Lin; Wang, Xiao-hui; Ruan, Jie; Sun, Xiao; Shan, Qun. Ursolic acid attenuates lipopolysaccharide-induced cognitive deficits in mouse brain through suppressing p38/NF-κB mediated inflammatory pathways. Neurobiology of Learning and Memory. 2011-09-01, 96 (2): 156–165. ISSN 1095-9564. PMID 21496491. doi:10.1016/j.nlm.2011.03.010.
15. Lu, Jun; Zheng, Yuan-Lin; Wu, Dong-Mei; Luo, Lan; Sun, Dong-Xu; Shan, Qun. Ursolic acid ameliorates cognition deficits and attenuates oxidative damage in the brain of senescent mice induced by D-galactose. Biochemical Pharmacology. 2007-10-01, 74 (7): 1078–1090. ISSN 0006-2952. PMID 17692828. doi:10.1016/j.bcp.2007.07.007.
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17. Jang, Sun-Mi; Yee, Sung-Tae; Choi, Jina; Choi, Myung-Sook; Do, Gyeong-Min; Jeon, Seon-Min; Yeo, Jiyoung; Kim, Myung-Joo; Seo, Kwon-Il. Ursolic acid enhances the cellular immune system and pancreatic beta-cell function in streptozotocin-induced diabetic mice fed a high-fat diet. International Immunopharmacology. 2009-01-01, 9 (1): 113–119. ISSN 1567-5769. PMID 19013541. doi:10.1016/j.intimp.2008.10.013.
18. Jeong, Ji-Woong; Shim, Jae-Jung; Choi, Il-Dong; Kim, Sung-Hwan; Ra, Jehyeon; Ku, Hyung Keun; Lee, Dong Eun; Kim, Tae-Youl; Jeung, Woonhee. Apple Pomace Extract Improves Endurance in Exercise Performance by Increasing Strength and Weight of Skeletal Muscle. Journal of Medicinal Food. 2015-12-01, 18 (12): 1380–1386. ISSN 1557-7600. PMID 26331671. doi:10.1089/jmf.2014.3401.
19. Li, Songtao; Liao, Xilu; Meng, Fanyu; Wang, Yemei; Sun, Zongxiang; Guo, Fuchuan; Li, Xiaoxia; Meng, Man; Li, Ying. Therapeutic role of ursolic acid on ameliorating hepatic steatosis and improving metabolic disorders in high-fat diet-induced non-alcoholic fatty liver disease rats. PLoS One. 2014-01-01, 9 (1): e86724. ISSN 1932-6203. PMC 3906058 . PMID 24489777. doi:10.1371/journal.pone.0086724.
20. The cytotoxic activity of ursolic acid derivatives. Eur J Med Chem. June 2005, 40 (6): 582–9. PMID 15922841. doi:10.1016/j.ejmech.2005.01.001.