The neuroprotective effect of Salvia przewalskii extract of total phenolic acids for the treatment of acute spinal cord injury in rats | [Pakistan Journal of Pharmaceutical Sciences • 2025]

Author(s):

1. Ying Zhang: Department of Pharmacy, The Affiliated Huaihai Hospital of Xuzhou Medical University (the 71st Group Army Hospital of the Chinese PLA Army), Xuzhou City, Jiangsu Province, China

2. Ying Guo: Department of Spine Surgery, The 928th Hospital of the Chinese PLA Joint Logistic Support Force, Haikou City, Hainan Province, China

3. Xun Tong: Department of Pharmacy, The Affiliated Huaihai Hospital of Xuzhou Medical University (the 71st Group Army Hospital of the Chinese PLA Army), Xuzhou City, Jiangsu Province, China

4. Zhonghai Zhou: Department of Pharmacy, The Affiliated Huaihai Hospital of Xuzhou Medical University (the 71st Group Army Hospital of the Chinese PLA Army), Xuzhou City, Jiangsu Province, China

5. Qian Hong: Department of Pharmacy, The Affiliated Huaihai Hospital of Xuzhou Medical University (the 71st Group Army Hospital of the Chinese PLA Army), Xuzhou City, Jiangsu Province, China

6. Bin Zhu: Department of Pharmacy, The Affiliated Huaihai Hospital of Xuzhou Medical University (the 71st Group Army Hospital of the Chinese PLA Army), Xuzhou City, Jiangsu Province, China

7. Lulu Wang: Department of Pharmacy, The Affiliated Huaihai Hospital of Xuzhou Medical University (the 71st Group Army Hospital of the Chinese PLA Army), Xuzhou City, Jiangsu Province, China

8. Hui Feng: Department of Pharmacy, The Affiliated Huaihai Hospital of Xuzhou Medical University (the 71st Group Army Hospital of the Chinese PLA Army), Xuzhou City, Jiangsu Province, China

9. Liaoxin Fang: Department of Pharmacy, The Affiliated Huaihai Hospital of Xuzhou Medical University (the 71st Group Army Hospital of the Chinese PLA Army), Xuzhou City, Jiangsu Province, China

10. Yang Yang: Department of Pharmacy, The Affiliated Huaihai Hospital of Xuzhou Medical University (the 71st Group Army Hospital of the Chinese PLA Army), Xuzhou City, Jiangsu Province, China

Abstract:

Salvia przewalskii Maxim. is a traditional Chinese herbal medicine which has long been used for the treatment of cardiovascular diseases in China. The current study aimed to investigate the neuroprotective effect of Salvia przewalskii extract of total phenolic acids (SPE) in a rat model of acute spinal cord injury (ASCI). Quantitative analysis of the active constituents in SPE by HPLC showed that rosmarinic acid accounted for 34.32% and salvianolic acid B for 4.27%. The experiment with the ASCI rat model demonstrated that SPE did not have significant adverse effects on body mass on day 1 and 3 after drug administration. In addition, SPE treatment significantly enhanced the BBB scores, improved the inclined plane angles and increased the serum levels of oxidative stress markers SOD and GSH in ASCI rats. Concurrently, it reduced the serum levels of MDA and inflammatory cytokines TNF-a, IL-1ß, IL-6, IL-17 and IL18. SPE also mitigated neuronal damage within the spinal cord tissue by minimizing hemorrhage and preserving neuronal integrity. Mechanistically, SPE ameliorated neuronal damage in the spinal cord by attenuating oxidative stress and inflammatory responses, thereby facilitating the recovery of motor function in ASCI rats.

Page(s): 2321-2332

DOI: 10.36721/PJPS.2025.38.6.REG.13560.1

Published: Journal: Pakistan Journal of Pharmaceutical Sciences, Volume: 38, Issue: 6, Year: 2025

Keywords:

Oxidative stress , Inflammatory , Neurological function , Neuroprotective effect , Acute spinal cord injury , Salvia przewalskii extract of total phenolic acids

References:

[1] Alizadeh A,Dyck SM,Karimi-Abdolrezaee S .2019 .Traumatic spinal cord injury: An overview of pathophysiology, models and acute injury mechanisms. Front, 10 : 282.

[2] Allison DJ,Ditor DS .2015 .Immune dysfunction and chronic inflammation following spinal cord injury. Spinal Cord, 53(1) : 14-18.

[3] Al-Nashash H,All AH H .2022 .Neuroprotective role of hypothermia in acute spinal cord injury. Biomedicines, 10(1) : 104.

[4] Chen S,Xie JD,Xie MT,Yang LN,Lin YF,Chen JB,Chen TF,Zeng KF,Tan ZB,Lu SM,Wang HJ,Yang B,Jiang WH,Zhang SW,Deng B,Liu B,Zhang J .2024 .Przewaquinone A inhibits angiotensin IIinduced endothelial diastolic dysfunction activation of AMPK. , 133 : 155885.

[5] Chen YF,Lu YQ,Gao WY,Fan BY,Ren FC,Shen CP .2025 .Anti-inflammatory abietane-type diterpenoids from the roots of Salvia przewalskii. Phytochemistry, 237 : 114523.

[6] Cheng TJ,Yang ZY .2003 .Comparison between Salvia przewalskii Maxim injection and S. miltiorrhiza Bunge injection on the protection on acute focal cerebral ischemia of rats and the effect against lipide peroxidation. Chin. J. Clin. Pharmacol, 8(1) : 23-26.

[7] Chu M,Feng L,Li YW .2003 .- an important resource in the Danshen type plants. Chin. Tradit. Herb. Drugs, 34(5) : 472-472.

[8] Dergham P,Ellezam B,Essagian C,Avedissian H,Lubell WD,McKerracher L WD .2002 .Rho signaling pathway targeted to promote spinal cord repair. J. Neurosci., 22(15) : 6570-6577.

[9] .1977 .Flora of China. IV-IV, 66 : 86-89.

[10] Fang P,Wang Y,Sun F,Lin H,Zhang X .2023 .Effects of albiflorin on oxidative stress and inflammatory responses in rats with acute spinal cord injury. Immun. Inflamm. Dis., 11(9) : e1015.

[11] Feng CP,Ding HX,Liang J,Liu YX,Yao SQ .2019 .Effect of rosmarinic acid on HepG2 cell apoptosis and autophagy inhibition. Pharmacol. Clin. Chin. Mater. Medica, 35(1) : 57-63.

[12] Fournier AE,Takizawa BT,Strittmatter SM .2003 .Rho kinase inhibition enhances axonal regeneration in the injured CNS. J. Neurosci., 23(4) : 1416-1423.

[13] Gao LP,Wei HL,Zhao HS,Xiao SY,Zheng RL .2005 .Antiapoptotic and antioxidant effects of rosmarinic acid in astrocytes. Pharmazie, 60(1) : 62-65.

[14] Guo R,Wang CL,Zhang T,Xu S,Qiao X,Zhang GS,Zhang Q .2025 .Structurally diverse abietane diterpenoids from the whole plants of Salvia przewalskii Maxim. With anti-inflammatory activity. Phytochemistry, 235 : 114456.

[15] Hong Q,Wei Y,Lian L,Wang Y,Wang LL,Yang Y .2023 .Protective effect of Salvia przewalskii extract of total phenolic acids on acute radiation induced bowel injury after ionizing radiation in rats. Chin. J. Hosp. Pharm., 43(15) : 1657-1662.

[16] Hong Q,Yang Y,Zhu B,Zhou ZH,Luo XM,Wang ZH,Wang LL .2021 .Protective effect and active mechanism research of Salvia przewalskii total phenolic acid extract against ionizing radiation damage in vascular endothelial cells. Mil. Med, 45(9) : 646-652.

[17] Hu X,Xu W,Ren Y,Wang Z,He X,Huang R,Ma B,Zhao J,Zhu R .2023 .Spinal cord injury: Molecular mechanisms and therapeutic interventions. Signal Transduct. Target. Ther., 8(1) : 245.

[18] Hung WL,Ho CT,Pan MH .2020 .Targeting the NLRP3 inflammasome in neuroinflammation: Health promoting effects of dietary phytochemicals in neurological disorders. Mol. Nutr, 64(4) : e1900550.

[19] Jiang WL,Chen XG,Qu GW,Yue XD,Zhu HB,Tian JW,Fu FH .2009 .Rosmarinic acid protects against experimental sepsis by inhibiting proinflammatory factor release and ameliorating hemodynamics. Shock, 32(6) : 608-613.

[20] Jiang XL,Liu B,Li JK,Lin YF,Zhu PL,Zhang Z,Wang Y,Deng B,Zhang JZ,Yung KKL .2025 .Przewaquinone A, as a natural STAT3 inhibitor, suppresses the growth of melanoma cells and induces autophagy. Phytomedicine, 142 : 156810.

[21] Joaquim AF,Daniel JW,Schroeder GD,Vaccaro AR .2020 .Neuroprotective agents as an adjuvant treatment in patients with acute spinal cord injuries: a qualitative systematic review of randomized trials. Clin. Spine Surg., 33(2) : 65-75.

[22] Korn T,Bettelli E,Oukka M,Kuchroo VK M .2009 .IL17 and Th17 cells. Annu. Rev. Immunol., 27 : 485-517.

[23] Lamien-Meda A,Nell M,Lohwasser U,Borner A,Franz C,Novak J .2010 .Investigation of antioxidant and rosmarinic acid variation in the sage collection of the genebank in Gatersleben. J. Agric. Food Chem, 58(6) : 3813-3819.

[24] Li X,Yang Y,Huang DD,Huang GH,Sun LN .2014 .Content determination of rosmarinic acid and salvianolic acid B from Salvia przewalskii and its extract. Chin. J. Hosp. Pharm., 34(19) : 1634-1638.

[25] Lin R,Wang WR,Liu JT,Yang GD,Han CJ .2006 .Protective effect of tanshinone IIA on human umbilical vein endothelial cell injured by hydrogen peroxide and its mechanism. J. Ethnopharmacol., 108(2) : 217-222.

[26] Lv C,Zhang T,Li K,Gao K K .2020 .Bone marrow mesenchymal stem cells improve spinal function of spinal cord injury in rats via TGF-β/Smads signaling pathway. Exp. Ther. Med, 19(6) : 3657-3663.

[27] Matkowski A,Zielińska S,Oszmiański J,LamerZarawska E,Bioresour S. verticillata L. .2008 .Antioxidant activity of extracts from leaves and roots of Salvia miltiorrhiza Bunge, S. przewalskii Maxim. , 99(16) : 7892-7896.

[28] Mehta P,Shah R,Lohidasan S,Mahadik KR .2015 .Pharmacokinetic profile of phytoconstituent(s) isolated from medicinal plants - A comprehensive review. J. Tradit. Complement. Med, 5(4) : 207-227.

[29] .2006 .Dictionary of traditional Chinese medicine. , : 643-650.

[30] .2016 .Drug user instructions for methylprednisolone sodium succinate for injection. China Medical Information Platform, : .

[31] Qiu BM,Wang P,Li J .2022 .Salprzesides A and B: two novel icetexane diterpenes with antiangiogenic activity from Salvia przewalskii Maxim. Nat. Prod. Res., 36(10) : 2479-2485.

[32] Rath N and Balain B .2017 .Spinal cord injury - The role of surgical treatment for neurological improvement. J. Clin. Orthop. Trauma, 8(2) : 99-102.

[33] Sánchez-Campillo M,Gabaldon JA,Castillo J,Benavente-García O,Baño MJD,Alcaraz M,Vicente V,Alvarez N,Lozano JA .2009 .Rosmarinic acid, a photo-protective agent against UV and other ionizing radiations. Food Chem, 47(2) : 386-392.

[34] Shang AJ,Yang Y,Wang HY,Tao BZ,Wang J,Wang ZF,Zhou DB .2017 .Spinal cord injury effectively ameliorated by neuroprotective effects of rosmarinic acid. Nutr, 20(3) : 172-179.

[35] Sherratt SCR,Villeneuve P,Durand E,Mason RP .1861 .Rosmarinic acid and its esters inhibit membrane cholesterol domain formation through an antioxidant mechanism based, in nonlinear fashion, on alkyl chain length. BBA-Biomembranes, : 550-555.

[36] Singh D .2022 .Astrocytic and microglial cells as the modulators of neuroinflammation in Alzheimer's disease. J. Neuroinflamm., 19(1) : 206.

[37] Srinivas BH,Rajesh A,Purohit AK .2017 .Factors affecting outcome of acute cervical spine injury: A prospective study. Asian J. Neurosurg., 12(3) : 416-423.

[38] Sun P,Zhao T,Zhou J,Qi H,Qian G H .2023 .Phosphodiesterase 4 inhibitor roflupram suppresses inflammatory responses using reducing inflammasome in microglia after spinal cord injury. Altern. Ther. Health Med, 29(7) : 340-347.

[39] Sunshine JE,Dagal A,Burns SP,Bransford RJ,Zhang F,Newman SF,Nair BG,Sharar SR .2017 .Methylprednisolone therapy in acute traumatic spinal cord injury: Analysis of a regional spinal cord model systems database. , 124(4) : 1200-1205.

[40] Tang Y,Le W Y .2016 .Differential roles of M1 and M2 microglia in neurodegenerative diseases. Mol. Neurobiol, 53(2) : 1181-1194.

[41] Tsehay Y,Weber-Levine C,Kim T,Chara A,Alomari S,Awosika T,Liu A,Ehresman J,Lehner K,Hwang B,Hersh AM,Suk I,Curry E,Aghabaglou F,Zeng YN,Manbachi A,Theodore N A .2022 .Advances in monitoring for acute spinal cord injury: A narrative review of current literature. , 22(8) : 1372-1387.

[42] Wang L,Yang H,Wang C,Shi X,Li K X .2019 .Rosmarinic acid inhibits proliferation and invasion of hepatocellular carcinoma cells SMMC 7721 via PI3K/AKT/mTOR signal pathway. Biomed, 120 : 109443.

[43] Wang Y,Duo D,Yan Y,He R,Wu X .2020 .Magnesium lithospermate B ameliorates hypobaric hypoxia-induced pulmonary arterial hypertension by inhibiting endothelial-to-mesenchymal transition and its potential targets. Biomed, 130 : 110560.

[44] Xiao Y,Xu W,Su W .2018 .NLRP3 inflammasome: A likely target for the treatment of allergic diseases. Clin. Exp. Allergy, 48(9) : 1080-1091.

[45] Xiong CX,Zong SH,Zeng GF,Wei B,Zhao YX .2011 .Establishment and evaluation of Allen's spinal cord injury model in rats. J. Guangxi Med, 28(2) : 215-217.

[46] Nunez Xu J,G Xu J .2023 .The NLRP3 inflammasome: Activation and regulation. Trends Biochem. Sci., 48(4) : 331-344.

[47] Yang Y,Li X,Zhu B,Sun SY,Sun LN .2015 .Study on quality standard of Salvia przewalskii extract of total phenolic acids. Lishizhen Med, 26(7) : 1590-1592.

[48] Yang Y,Lu W,Wu Z,Chen W .2017 .A new diterpenoid from Salvia przewalskii. Rec. Nat. Prod, 11(4) : 416-420.

[49] Yang Y,Luo XM,Wang DD,Wang LL,Zhou ZH,Zhu B .2020 .Protective effect of Salvia przewalskii total phenolic acid extract on radiation damage in rats. J. Chin. PLA, 32(2) : 8-15.

[50] Yang Y,Zhang F,Cai F,Sun LN,Chen WS .2008 .Advances in studies on chemical constituents and pharmacological effects of Salvia przewalskii Maxim. J. Chin. Med, 31(5) : 787-790.

[51] Yang Y,Zhu B,Wu ZJ,Chen WS,Sun LN .2012 .Effects of Salvia przewalskii Maxim. extract on whole blood viscosity in normal rats and its diuresis in waterloaded rats. Chin. J. Hosp. Pharm., 32(10) : 751-754.

[52] Zhang GP,Zhang HH,Zhang WD .2012 .The influence of panax notoginsenosides on the sloping plate experiment score in rats with spinal cord injury. China Mod, 50(1) : 9-10.

[53] Zhang Y,Akao T,Nakamura N,Hattori M,Yang XW,Duan CL,Liu JX .2004 .Magnesium lithospermate B is excreted rapidly into rat bile mostly as methylated metabolites, which are potent antioxidants. Drug Metab, 32(7) : 752-757.

[54] Zhao GR,Zhang HM,Ye TX,Xiang ZJ,Yuan YJ,Guo ZX,Zhao LB .2008 .Characterization of the radical scavenging and antioxidant activities of danshensu and salvianolic acid B. Food Chem, 46(1) : 73-81.

[55] Zhao JB .2003 .Study and application evaluation on Gansudanshen (Salvia przewalskii Maxim. J. Chin. Med, 26(7) : 529-531.

[56] Zhao K,Qian C,Qi L,Li Q,Zhao C,Zhang J,Han G,Xia L,El-Bahy ZM,Gu J,Helal MH,Yan Z,Guo Z,Shi Z Z .2024 .Modified acid polysaccharide derived from Salvia przewalskii with excellent wound healing and enhanced bioactivity. Int. J. Biol. Macromol, 263 : 129803.

[57] Zhu B,Yang Y,Jiang P Y .2016 .Content determination of rosmarinic acid and salvianolic acid B in Salvia przewalskii and total phenolic acid extract by NIRDRS. China Pharmacist, 19(1) : 69-60.

[58] Zong S,Zeng G,Fang Y,Peng J,Tao Y,Li K,Zhao J .2014 .The role of IL-17 promotes spinal cord neuroinflammation via activation of the transcription factor STAT3 after spinal cord injury in the rat. Mediators Inflamm, : 786947.

[59] Zong S,Zeng G,Wei B,Xiong C,Zhao Y .2012 .Beneficial effect of interleukin-1 receptor antagonist protein on spinal cord injury recovery in the rat. Inflammation, 35(2) : 520-526.

Citations

Downloads

Views