Efficacy of curcumin in the treatment of oral submucous fibrosis: a Meta-analysis

doi:10.7518/hxkq.2021.02.011

Abstract

Abstract: Objective

This study was performed to review the efficacy of curcumin in the treatment of oral submucous fibrosis systematically.

Methods

We searched seven databases, including Web of Science, PubMed, EBSCO, The Cochrane Library, CNKI, WanFang Data, and VIP, to obtain randomized controlled trials related to the treatment of oral submucous fibrosis by curcumin. Each database was searched from inception to 30 June 2019. RevMan 5.3 software was used for the meta-analysis.

Results

Six randomized controlled trials involving 350 patients were included in this study. Meta-analysis showed that curcumin can increase the maximal mouth opening and improve burning sensation compared with placebo treatment. Curcumin was not as effective as the controls in achieving maximal mouth opening after 1 month of treatment. However, no statistically significant difference was observed between the treatments from 2 months to 6 months. Curcumin significantly improved burning sensation compared with the controls after 3 months of treatment. No statistically significant diffe-rence in burning sensation was observed between the curcumin and control groups after 1, 2, and 6 months of treatment.

Conclusion

The current evidence shows that curcumin is an effective treatment for improving maximal mouth opening and burning sensation in patients with oral submucous fibrosis. Given the limited number and low quality of the included studies, however, more high-quality studies are needed to verify these findings.

Key words: oral submucous fibrosis, curcumin, Meta-analysis, evidence-based medicine

CLC Number:

R 781.5

Guo Jincai, Xie Hui, Wu Hao, Tong Tiejun. Efficacy of curcumin in the treatment of oral submucous fibrosis: a Meta-analysis[J]. West China Journal of Stomatology, 2021, 39(2): 195-202.

Figures/Tables 8

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References 36

1	Liu J, Chen F, Wei Z, et al. Evaluating the efficacy of pentoxifylline in the treatment of oral submucous fibrosis: a meta-analysis[J]. Oral Dis, 2018, 24(5): 706-716.
2	Al-Maweri SA, Ashraf S, Lingam AS, et al. Aloe vera in treatment of oral submucous fibrosis: a systematic review and meta-analysis[J]. J Oral Pathol Med, 2019, 48(2): 99-107.
3	Trivedy C, Baldwin D, Warnakulasuriya S, et al. Copper content in Areca catechu (betel nut) products and oral submucous fibrosis[J]. Lancet, 1997, 349(9063): 1447.
4	Ray JG, Chatterjee R, Chaudhuri K. Oral submucous fibrosis: a global challenge. Rising incidence, risk factors, management, and research priorities[J]. Periodontol 2000, 2019, 80(1): 200-212.
5	Kondaiah P, Pant I, Khan I. Molecular pathways regula-ted by areca nut in the etiopathogenesis of oral submucous fibrosis[J]. Periodontol 2000, 2019, 80(1): 213-224.
6	Zhang SS, Li WH, Gao YJ, et al. Betel-quid and oral submucous fibrosis: a cross-sectional study in Hunan Province, China[J]. J Oral Pathol Med, 2012, 41(10): 748-754.
7	唐杰清, 翦象福, 高明亮, 等. 中国湖南湘潭口腔黏膜下纤维性变的流行病学研究[J]. 中国医师杂志, 2015, 17(9): 1290-1295.
	Tang JQ, Jian XF, Gao ML, et al. Epidemiological survey of oral submucous fibrosis in Xiangtan City, Hunan Province, China[J]. J Chin Physic, 2015, 17(9): 1290-1295.
8	Yang SF, Wang YH, Su NY, et al. Changes in prevalence of precancerous oral submucous fibrosis from 1996 to 2013 in Taiwan: a nationwide population-based retrospective study[J]. J Formos Med Assoc, 2018, 117(2): 147-152.
9	Pindborg JJ, Mehta FS, Gupta PC, et al. Prevalence of oral submucous fibrosis among 50, 915 Indian villagers[J]. Br J Cancer, 1968, 22(4): 646-654.
10	Kumar S, Debnath N, Ismail MB, et al. Prevalence and risk factors for oral potentially malignant disorders in Indian population[J]. Adv Prev Med, 2015, 2015: 208519.
11	郭锦材, 谢辉. 中医药治疗口腔黏膜下纤维化的临床研究进展[J]. 口腔医学研究, 2019, 35(5): 423-426.
	Guo JC, Xie H. Research progress of traditional Chinese medicine in treatment of oral submucous fibrosis[J]. J Oral Sci Res, 2019, 35(5): 423-426.
12	Chole RH, Gondivkar SM, Gadbail AR, et al. Review of drug treatment of oral submucous fibrosis[J]. Oral Oncol, 2012, 48(5): 393-398.
13	刘锦丽, 陈方曼, 江潞. 口腔黏膜下纤维性变的药物治疗进展[J]. 国际口腔医学杂志, 2017, 44(3): 325-331.
	Liu JL, Chen FM, Jiang L. Drug management of oral submucous fibrosis[J]. Int J Stomatol, 2017, 44(3): 325-331.
14	翦新春, 郑廉, 朱蓉, 等. 曲安奈德和丹参酮注射液治疗口腔黏膜下纤维化的效果评价[J]. 中华口腔医学杂志, 2017, 52(1): 16-21.
	Jian XC, Zheng L, Zhu R, et al. Clinical effectiveness of salvianolic acid B and triamcinolone acetonide in treatment of oral submucous fibrosis[J]. Chin J Stomatol, 2017, 52(1): 16-21.
15	郭锦材, 谢辉. 天然药物提取物治疗口腔黏膜下纤维性变的临床研究进展[J]. 临床口腔医学杂志, 2018, 34(11): 692-695.
	Guo JC, Xie H. The clinical research progress of natural drug extracts in the treatment of oral submucous fibrosis[J]. J Clin Stomatol, 2018, 34(11): 692-695.
16	Piyush P, Mahajan A, Singh K, et al. Comparison of the-rapeutic response of lycopene and curcumin in oral submucous fibrosis: a randomized controlled trial[J]. Oral Dis, 2019, 25(1): 73-79.
17	Saran G, Umapathy D, Misra N, et al. A comparative study to evaluate the efficacy of lycopene and curcumin in oral submucous fibrosis patients: a randomized clinical trial[J]. Indian J Dent Res, 2018, 29(3): 303-312.
18	Ara SA, Mudda J, Lingappa A, et al. Efficacy of curcu-min in oral submucous fibrosis—a randomized controlled clinical trial[J]. Int J Pharm Sci Res, 2018, 9(12): 5277-5286.
19	Kopuri RKC, Chakravarthy C, Sunder S, et al. A comparative study of the clinical efficacy of lycopene and curcumin in the treatment of oral submucous fibrosis using ultrasonography[J]. J Int Oral Health, 2016, 8(6): 687-691.
20	Hazarey VK, Sakrikar AR, Ganvir SM. Efficacy of curcumin in the treatment for oral submucous fibrosis—a randomized clinical trial[J]. J Oral Maxillofac Pathol, 2015, 19(2): 145-152.
21	Yadav M, Aravinda K, Saxena VS, et al. Comparison of curcumin with intralesional steroid injections in oral submucous fibrosis—a randomized, open-label interventio-nal study[J]. J Oral Biol Craniofac Res, 2014, 4(3): 169-173.
22	夏丽, 李冰. 姜黄素在抗口腔黏膜下纤维化中的作用研究进展[J]. 解放军医学杂志, 2019, 44(4): 357-360.
	Xia L, Li B. Research progress of curcumin in anti-oral submucous fibrosis[J]. Med J Chin PLA, 2019, 44(4): 357-360.
23	Al-Maweri SA. Efficacy of curcumin for management of oral submucous fibrosis: a systematic review of randomized clinical trials[J]. Oral Surg Oral Med Oral Pathol Oral Radiol, 2019, 127(4): 300-308.
24	Mirzaei H, Shakeri A, Rashidi B, et al. Phytosomal curcumin: a review of pharmacokinetic, experimental and clinical studies[J]. Biomedecine Pharmacother, 2017, 85: 102-112.
25	Ara SA, Mudda JA, Lingappa A, et al. Research on curcumin: a meta-analysis of potentially malignant disorders[J]. J Cancer Res Ther, 2016, 12(1): 175-181.
26	Shih YH, Wang TH, Shieh TM, et al. Oral submucous fibrosis: a review on etiopathogenesis, diagnosis, and the-rapy[J]. Int J Mol Sci, 2019, 20(12): E2940.
27	Arakeri G, Rai KK, Hunasgi S, et al. Oral submucous fibrosis: an update on current theories of pathogenesis[J]. J Oral Pathol Med, 2017, 46(6): 406-412.
28	Zhang SS, Gong ZJ, Li WH, et al. Antifibrotic effect of curcumin in TGF-β 1-induced myofibroblasts from human oral mucosa[J]. Asian Pac J Cancer Prev, 2012, 13(1): 289-294.
29	Deng YT, Chen HM, Cheng SJ, et al. Arecoline-stimula-ted connective tissue growth factor production in human buccal mucosal fibroblasts: modulation by curcumin[J]. Oral Oncol, 2009, 45(9): e99-e105.
30	Rai B, Kaur J, Jacobs R, et al. Possible action mechanism for curcumin in pre-cancerous lesions based on serum and salivary markers of oxidative stress[J]. J Oral Sci, 2010, 52(2): 251-256.
31	Gupta S, Ghosh S, Gupta S, et al. Effect of curcu-min on the expression of p53, transforming growth factor-β, and inducible nitric oxide synthase in oral submucous fibrosis: a pilot study[J]. J Investig Clin Dent, 2017, 8(4). doi: 10.1111/jicd.12252.
32	Chang MC, Chen YJ, Chang HH, et al. Areca nut components affect COX-2, cyclin B1/cdc25C and keratin expression, PGE2 production in keratinocyte is related to reactive oxygen species, CYP1A1, Src, EGFR and Ras signaling[J]. PLoS One, 2014, 9(7): e101959.
33	Farhood B, Mortezaee K, Goradel NH, et al. Curcumin as an anti-inflammatory agent: implications to radiothe-rapy and chemotherapy[J]. J Cell Physiol, 2019, 234(5): 5728-5740.
34	Guo JC, Xie H, Wu H, et al. Efficacy of lycopene in the treatment of oral submucous fibrosis: a meta-analysis of randomized controlled trials[J]. J Evid Based Dent Pract, 2020, 20(4): 101471.
35	Xie H, Guo JC, Tan BY, et al. Efficacy of salvia miltiorrhiza injection combined with steroids in the treatment of oral submucous fibrosis: a meta-analysis of rando-mized controlled trials[J]. Medicine (Baltimore), 2019, 98(27): e16339.
36	Guo JC, Xie H, Mao S, et al. Efficacy of hyaluronidase combined with corticosteroids in treatment of oral submucous fibrosis: a meta-analysis of randomized controlled clinical trials[J]. J Oral Pathol Med, 2020, 49(4): 311-319.

步骤	检索策略
1	“Oral submucous fibrosis”[MeSH] OR “OSF” [MeSH] OR “OSMF” [MeSH]
2	“Atrophia idiopathica mucosae oris” [Title/Abstract] OR “Diffuse oral submucous fibrosis” [Title/Abstract] OR “Submucous fibrosis of the palate and pillars” OR “Idiopathic scleroderma of the mouth” [Title/Abstract] OR “Asian side-ropenic dysphagia” [Title/Abstract] OR “Sclerosing stomatitis” [Title/Abstract] OR “Idiopathic palatal fibrosis” [Title/Abstract] OR “Juxta-epithelial fibrosis” [Title/Abstract]
3	1 OR 2
4	“Curcumin” [Title/Abstract] OR “Turmeric” [Title/Abstract]
5	3 AND 4

纳入研究	例数 (T/C)	年龄/岁		性别（男/女）		干预措施		疗程/月	随访时间/月	结局指标
纳入研究	例数 (T/C)	年龄/岁		性别（男/女）		T	C	疗程/月	随访时间/月	结局指标
Piyush 等^[16]	30/30	17~60（32）		53/7		姜黄素300 mg, po,bid	番茄红素8 mg,po, bid	6	3	①② ③④
Saran 等^[17]	30/30	T:27.9±8.66	C:26.00±6.43	T:21/9	C:19/11	姜黄素300 mg, po,tid	番茄红素4 mg,po, bid	3	1	①②
Ara 等^[18]	50/50	T:25.42±7.38	C:25.44±5.43	T:45/5	C:48/2	姜黄素500 mg, po,bid	安慰剂500 mg,po, bid	6	0	①② ③④
Kopuri 等^[19]	15/15	不详		不详		姜黄素400 mg, po,bid	番茄红素4mg,po, bid	3	0	①② ⑤⑥
Hazarey等^[20]	15/15	18~50		不详		姜黄素400 mg, po,tid	局部涂氯倍他索乳膏, tid	3	6	①②
Yadav等^[21]	20/20	T:37.9±10.5	C:37.9±10.5	T:15/5	C:16/4	姜黄素300 mg, po,qd	地塞米松4 mg+透明质酸酶1 500 IU局部注射, 1周1次	3	3	①④

纳入研究	随机方法	分配隐藏	盲法		结果数据完整性	选择性报告研究结果	其他偏倚
纳入研究	随机方法	分配隐藏	研究和受试者	结果评价者	结果数据完整性	选择性报告研究结果	其他偏倚
Piyush等^[16]	计算机随机	不透明信封	双盲	盲法	完整	低风险	不清楚
Saran等^[17]	鱼缸法	不清楚	双盲	盲法	完整	低风险	不清楚
Ara等^[18]	随机数字表法	不清楚	单盲	盲法	完整	低风险	不清楚
Kopuri等^[19]	不清楚	不清楚	不清楚	不清楚	完整	低风险	不清楚
Hazarey等^[20]	不清楚	不清楚	不清楚	不清楚	完整	低风险	不清楚
Yadav等^[21]	随机数字表法	不清楚	不清楚	不清楚	完整	低风险	不清楚

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