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BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2023

Open Access 01-12-2023 | Research

Research on the wound healing effect of Shengji Huayu Formula ethanol extract-derived fractions in streptozotocin-induced diabetic ulcer rats

Authors: Jing-Ting Zhang, Min-Feng Wu, Ming-Hua Ma, Liang Zhao, Jian-Yong Zhu, Hua Nian, Fu-Lun Li

Published in: BMC Complementary Medicine and Therapies | Issue 1/2023

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Abstract

Background

Diabetic ulcer is a common complication of diabetes. It is characterized by a long-term disease course and high recurrence rate. Shengji Huayu Formula (SHF) is an effective formula for treating diabetic ulcers. However, the specific effective parts of SHF remain unclear. Clarifying the active polar site of SHF would be helpful to refine research on the components in SHF that promote wound healing. This research aims to focus on evaluating the activity of polar fractions.

Methods

A diabetic rat model was established by intraperitoneally injecting streptozotocin (STZ) and was adopted to confirm the therapeutic effect of SHF. Four different polarity parts were extracted from SHF and prepared into a cream to evaluate the activity. High-performance liquid chromatography (HPLC) was used to detect chemical constituents in chloroform extracts.

Results

It was discovered that dracorhodin, aloe-emodin, rhein, imperatorin, emodin, isoimperatorin, chrysophanol, physcion, and tanshinone IIA were the main components of the chloroform extract from SHF. The results revealed that chloroform extract could effectively accelerate diabetic wound healing by promoting collagen regeneration and epidermal repair. Chloroform extract of SHF could stimulate the generation of vascular endothelial growth factor (VEGF). The results are also indicated that the effective active fraction was the chloroform part, and the method of detecting the main chemical constituents in the active part was successfully established.

Conclusion

SHF could improve diabetic ulcers by promoting granulation tissue synthesis. In this study, four polar parts (petroleum ether, chloroform, ethylacetate, n-butanol) were extracted from a 95% ethanol extract. In contrast, chloroform polar parts showed a higher wound closure rate, stimulated more collagen regeneration and promoted more production of vascular endothelial cells. In conclusion, the chloroform extract of SHF was the effective polar part in ameliorating diabetic wound healing.
Literature
1.
Zhang P, Lu J, Jing Y, Tang S, Zhu D, Bi Y. Global epidemiology of diabetic foot ulceration: a systematic review and meta-analysis. Ann Med. 2017;49(2):106–16.PubMedCrossRef
2.
Cho NH, Shaw JE, Karuranga S, Huang Y, da Rocha Fernandes JD, Ohlrogge AW, Malanda B. IDF diabetes atlas: global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract. 2018;138:271–81.PubMedCrossRef
3.
Jiang Y, Wang X, Xia L, Fu X, Xu Z, Ran X, Yan L, Li Q, Mo Z, Yan Z, et al. A cohort study of diabetic patients and diabetic foot ulceration patients in China. Wound Repair Regen. 2015;23(2):222–30.PubMedCrossRef
4.
Shan GQ, Zhang YN, Ma J, Li YH, Zuo DM, Qiu JL, Cheng B, Chen ZL. Evaluation of the effects of homologous platelet gel on healing lower extremity wounds in patients with diabetes. Int J Low Extrem Wounds. 2013;12(1):22–9.PubMedCrossRef
5.
Couture M. A single-center, retrospective study of cryopreserved umbilical cord for wound healing in patients suffering from chronic wounds of the foot and ankle. Wounds. 2016;28(7):217–25.PubMed
6.
Zhang J, Zhou R, Xiang C, Jia Q, Wu H, Yang H. Huangbai liniment accelerated wound healing by activating Nrf2 signaling in diabetes. Oxid Med Cell Longev. 2020;2020:4951820.PubMedPubMedCentral
7.
Wu M, Huang J, Shi J, Shi L, Zeng Q, Wang H. Ruyi Jinhuang powder accelerated diabetic ulcer wound healing by regulating Wnt/beta-catenin signaling pathway of fibroblasts in vivo and in vitro. J Ethnopharmacol. 2022;293:115321.PubMedCrossRef
8.
Jiang JS, Zhang Y, Luo Y, Ru Y, Luo Y, Fei XY, Song JK, Ding XJ, Zhang Z, Yang D, et al. The identification of the biomarkers of Sheng-Ji Hua-Yu formula treated diabetic wound healing using modular pharmacology. Front Pharmacol. 2021;12:726158.PubMedPubMedCentralCrossRef
9.
Xiang Y, Kuai L, Ru Y, Jiang J, Li X, Li F, Chen Q, Li B. Transcriptional profiling and circRNA-miRNA-mRNA network analysis identify the biomarkers in Sheng-ji Hua-yu formula treated diabetic wound healing. J Ethnopharmacol. 2021;268:113643.PubMedCrossRef
10.
Ru Y, Zhang Y, Xiang YW, Luo Y, Luo Y, Jiang JS, Song JK, Fei XY, Yang D, Zhang Z, et al. Gene set enrichment analysis and ingenuity pathway analysis to identify biomarkers in Sheng-ji Hua-yu formula treated diabetic ulcers. J Ethnopharmacol. 2022;285:114845.PubMedCrossRef
11.
Kuai L, Zhang JT, Deng Y, Xu S, Xu XZ, Wu MF, Guo DJ, Chen Y, Wu RJ, Zhao XQ, et al. Sheng-ji Hua-yu formula promotes diabetic wound healing of re-epithelization via Activin/Follistatin regulation. BMC Complement Altern Med. 2018;18(1):32.PubMedPubMedCentralCrossRef
12.
Lu Y, Ding X, Qi F, Ru Y, Kuai L, Chen S, Yang Y, Li X, Li F, Li B, et al. Quyu Shengji formula facilitates diabetic wound healing via inhibiting the expression of prostaglandin transporter. Evid Based Complement Alternat Med. 2021;2021:8849935.PubMedPubMedCentralCrossRef
13.
Zhang J, Minghua MA, Minfeng WU, Wang X, Fulun LI, Hua N. Therapeutic effect of 95% ethanol extract of Shengji Huayu formula on diabetic wound. Chin J Modern Appl Pharm. 2017;34(10):1369–72.
14.
Ming Z, Lv XY, Jing L, Xu ZG, Chen L. The characterization of high-fat diet and multiple low-dose streptozotocin induced type 2 diabetes rat model. Exp Diabetes Res. 2008;2008(6):704045.
15.
Isei T, Abe M, Nakanishi T, Matsuo K, Yamasaki O, Asano Y, Ishii T, Ito T, Inoue Y, Imafuku S, et al. The wound/burn guidelines - 3: guidelines for the diagnosis and treatment for diabetic ulcer/gangrene. J Dermatol. 2016;43(6):591–619.PubMedCrossRef
16.
Piotto C, Julier Z, Martino MM. Immune regulation of tissue repair and regeneration via miRNAs-New therapeutic target. Front Bioeng Biotechnol. 2018;6:98.PubMedPubMedCentralCrossRef
17.
Wichaiyo S, Lax S, Montague SJ, Li Z, Grygielska B, Pike JA, Haining EJ, Brill A, Watson SP, Rayes J. Platelet glycoprotein VI and C-type lectin-like receptor 2 deficiency accelerates wound healing by impairing vascular integrity in mice. Haematologica. 2019;104(8):1648–60.PubMedPubMedCentralCrossRef
18.
Du Y, Ren P, Wang Q, Jiang SK, Zhang M, Li JY, Wang LL, Guan DW. Cannabinoid 2 receptor attenuates inflammation during skin wound healing by inhibiting M1 macrophages rather than activating M2 macrophages. J Inflamm (Lond). 2018;15:25.PubMedCrossRef
19.
Zhang J, Wu M, Ma M, Zhu Q, Li G, Nian H. Study advances in traditional chinese medicines used in diabetic refractory wound. Chin Pharm. 2015;18(12):2138–40.
20.
Kreimendahl F, Marquardt Y, Apel C, Bartneck M, Zwadlo-Klarwasser G, Hepp J, Jockenhoevel S, Baron JM. Macrophages significantly enhance wound healing in a vascularized skin model. J Biomed Mater Res A. 2019;107(6):1340–50.PubMedCrossRef
21.
Wu M, Deng Y, Li S, Chen Y, Guo D, Jin X, Xu Q, Li B, Li F. The immunoregulatory effects of traditional Chinese medicine on psoriasis via its action on interleukin: advances and considerations. Am J Chin Med. 2018;46(4):739–50.PubMedCrossRef
22.
Wu M, Li Y, Guo D, Kui G, Li B, Deng Y, Li F. Microbial diversity of chronic wound and successful management of traditional Chinese medicine. Evid Based Complement Alternat Med. 2018;2018:9463295.PubMedPubMedCentralCrossRef
23.
Wang G, Wang Y, Wang F, Ding Y, Kang Y, Dong Y, Lv P, Xu X. Lower limb nonhealing ulcers associated with chronic diabetes: a case series. Wounds. 2019;31(1):7–14.PubMed
24.
Li FL, Deng H, Wang HW, Xu R, Chen J, Wang YF, Li X, Fan B, Li B. Effects of external application of Chinese medicine on diabetic ulcers and the expressions of beta-catenin, c-myc and K6. Chin J Integr Med. 2011;17(4):261–6.PubMedCrossRef
25.
Li FL, Wang YF, Li X, Li F, Xu R, Chen J, Geng L, Li B. Characteristics and clinical managements of chronic skin ulcers based on traditional chinese medicine. Evid Based Complement Alternat Med. 2012;2012:930192.PubMedPubMedCentralCrossRef
26.
Kulkarni M, O’Loughlin A, Vazquez R, Mashayekhi K, Rooney P, Greiser U, O’Toole E, O’Brien T, Malagon MM, Pandit A. Use of a fibrin-based system for enhancing angiogenesis and modulating inflammation in the treatment of hyperglycemic wounds. Biomaterials. 2014;35(6):2001–10.PubMedCrossRef
27.
28.
Zhou Q, Jiang S, Ma K, Li C. Expression of a novel recombinant fusion protein BVN-Tbeta4 and its effects on diabetic wound healing. J Biosci Bioeng. 2014;118(3):341–3.PubMedCrossRef
29.
Luo X, Huang P, Yuan B, Liu T, Lan F, Lu X, Dai L, Liu Y, Yin H. Astragaloside IV enhances diabetic wound healing involving upregulation of alternatively activated macrophages. Int Immunopharmacol. 2016;35:22–8.PubMedCrossRef
30.
Park JY, Kwak JH, Kang KS, Jung EB, Lee DS, Lee S, Jung Y, Kim KH, Hwang GS, Lee HL, et al. Wound healing effects of deoxyshikonin isolated from Jawoongo: in vitro and in vivo studies. J Ethnopharmacol. 2017;199:128–37.PubMedCrossRef
31.
Park JY, Shin MS, Hwang GS, Yamabe N, Yoo JE, Kang KS, Kim JC, Lee JG, Ham J, Lee HL. Beneficial effects of deoxyshikonin on delayed wound healing in diabetic mice. Int J Mol Sci. 2018;19(11):3660.PubMedPubMedCentralCrossRef
32.
Xiong Z, Huo M, Jia Y, Zhou C, Ma X, Yin H, Jiang X, Yu W. Dracorhodin perchlorate regulates the expression of inflammatory cytokines through the TLR4 pathway and improves skin wound healing in diabetic rats. Evid Based Complement Alternat Med. 2022;2022:9050686.PubMedPubMedCentralCrossRef
33.
Lu CC, Yang JS, Chiu YJ, Tsai FJ, Hsu YM, Yin MC, Juan YN, Ho TJ, Chen HP. Dracorhodin perchlorate enhances wound healing via beta-catenin, ERK/p38, and AKT signaling in human HaCaT keratinocytes. Exp Ther Med. 2021;22(2):822.PubMedPubMedCentralCrossRef
34.
Jiang XW, Qiao L, Liu L, Zhang BQ, Wang XW, Han YW, Yu WH. Dracorhodin perchlorate accelerates cutaneous wound healing in wistar rats. Evid Based Complement Alternat Med. 2017;2017:8950516.PubMedPubMedCentralCrossRef
35.
Jiang X, Liu L, Qiao L, Zhang B, Wang X, Han Y, Yu W. Dracorhodin perchlorate regulates fibroblast proliferation to promote rat’s wound healing. J Pharmacol Sci. 2018;136(2):66–72.PubMedCrossRef
36.
Yin C, Han X, Lu Q, Qi X, Guo C, Wu X. Rhein incorporated silk fibroin hydrogels with antibacterial and anti-inflammatory efficacy to promote healing of bacteria-infected burn wounds. Int J Biol Macromol. 2022;201:14–9.PubMedCrossRef
37.
Li L, Lin Y, Bin G, Shu Q, Chen D, Shan Y, Wang S, Huang B, Wang J, Tang Q. MEBT/MEBO promoted chronic non-healing cutaneous wound by modulating the P13K-Akt-mTOR signaling pathway. Chin J Integr Tradit Western Med. 2019;39(5):583–90.
38.
Takagi N, Kawakami K, Kanno E, Tanno H, Takeda A, Ishii K, Imai Y, Iwakura Y, Tachi M. IL-17A promotes neutrophilic inflammation and disturbs acute wound healing in skin. Exp Dermatol. 2017;26(2):137–44.PubMedCrossRef
39.
Seo E, Lim JS, Jun JB, Choi W, Hong IS, Jun HS. Exendin-4 in combination with adipose-derived stem cells promotes angiogenesis and improves diabetic wound healing. J Transl Med. 2017;15(1):35.PubMedPubMedCentralCrossRef
40.
Zhou J, Ni M, Liu X, Ren Z, Zheng Z. Curcumol promotes Vascular Endothelial Growth Factor (VEGF)-mediated diabetic wound healing in streptozotocin-induced hyperglycemic rats. Med Sci Monit. 2017;23:555–62.PubMedPubMedCentralCrossRef
41.
Guodong L, Chung-Nga K, Dan L, Chao Y, Wanhe W, Guan-Jun Y, Carmelo D, Vincent K, Yaozu X, Ligen Lin, Dik-Lung M, Chung-Hang L. A small molecule HIF-1α stabilizer that accelerates diabetic wound healing. Nat Commun. 2021;12(1):3363.CrossRef
42.
Ratklao S, Anh Q, Makio H, Kentaro A, Satoko S, Akira W, Shuh N, Dean T. Single-cell RNA sequencing identifies a migratory keratinocyte subpopulation expressing THBS1 in epidermal wound healing. iScience. 2022;25(4):104130.CrossRef
43.
Nam J, Lee H, Bae HC, Kim J, Jeong S, Ryu W, Son S. Chloroform induces HIF-1α-dependent VEGF expression in human keratinocytes. Mol Cell Toxicol. 2013;9(4):335–40.CrossRef
44.
Jiang X, Qiao L, Liu L, Zhang B, Wang X, Han Y, Yu W. Dracorhodin perchlorate accelerates cutaneous wound healing in wistar rats. Evid-based Compl Alt. 2017;2017:8950516.CrossRef
45.
Koken G, Abamor E, Allahverdiyev A, Karaoz E. Wharton jelly derived mesenchymal stem cell’s exosomes demonstrate significant antileishmanial and wound healing effects in combination with aloe-emodin: an in vitro study. J Pharm Sci. 2022;111(12):3232–42.PubMedCrossRef
46.
Li J, Wang C, Han X, Liu S, Gao X, Guo C, Wu X. Aramid nanofibers-reinforced rhein fibrous hydrogels as antibacterial and anti-inflammatory burn wound dressings. ACS Appl Mater Interfaces. 2022;14(40):45167–77.PubMedCrossRef
47.
48.
Qu K, Cha H, Ru Y, Que H, Xing M. Buxuhuayu decoction accelerates angiogenesis by activating the PI3K-Akt-eNOS signalling pathway in a streptozotocin-induced diabetic ulcer rat model. J Ethnopharmacol. 2021;273:113824.PubMedCrossRef
Metadata
Title
Research on the wound healing effect of Shengji Huayu Formula ethanol extract-derived fractions in streptozotocin-induced diabetic ulcer rats
Authors
Jing-Ting Zhang
Min-Feng Wu
Ming-Hua Ma
Liang Zhao
Jian-Yong Zhu
Hua Nian
Fu-Lun Li
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2023
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-023-03894-0

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